Identification of artesunate as a specific activator of ferroptosis in pancreatic cancer cells

Eling, Nils; Reuter, Lukas; Hazin, John; Hamacher-Brady, Anne; Brady, Nathan R.

doi:10.18632/oncoscience.160

Cited by 530Ferroptosis and cancer prognosisCell death mechanisms and regulationPancreatic and Hepatic Oncology Research

Identification of artesunate as a specific activator of ferroptosis in pancreatic cancer cells

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Eling, Nils, Reuter, Lukas, Hazin, John, Hamacher-Brady, Anne, Brady, Nathan R.·2015·Oncoscience

DOI 10.18632/oncoscience.160PMC PMC4468338

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Abstract

Oncogenic KRas reprograms pancreatic ductal adenocarcinoma (PDAC) cells to states which are highly resistant to apoptosis. Thus, a major preclinical goal is to identify effective strategies for killing PDAC cells. Artesunate (ART) is an anti-malarial that specifically induces programmed cell death in different cancer cell types, in a manner initiated by reactive oxygen species (ROS)-generation. In this study we demonstrate that ART specifically induced ROS- and lysosomal iron-dependent cell death in PDAC cell lines. Highest cytotoxicity was obtained in PDAC cell lines with constitutively-active KRas, and ART did not affect non-neoplastic human pancreatic ductal epithelial (HPDE) cells. We determined that ART did not induce apoptosis or necroptosis. Instead, ART induced ferroptosis, a recently described mode of ROS- and iron-dependent programmed necrosis which can be activated in Ras-transformed cells. Co-treatment with the ferroptosis inhibitor ferrostatin-1 blocked ART-induced lipid peroxidation and cell death, and increased long-term cell survival and proliferation. Importantly, analysis of PDAC patient mRNA expression indicates a dependency on antioxidant homeostasis and increased sensitivity to free intracellular iron, both of which correlate with Ras-driven sensitivity to ferroptosis. Overall, our findings suggest that ART activation of ferroptosis is an effective, novel pathway for killing PDAC cells.

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Artemisinin derivatives induce iron-dependent cell death, specifically ferroptosis.
“Of note, artemisinin derivatives have been reported to induce iron-dependent cell death, and specifically ferroptosis”
From Ferroptosis: Death by Lipid Peroxidation (2016) · cites this paper as [85]

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Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590 · see citing works
Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
Dixon, S. J., Lemberg, K. M., Lamprecht, M. R., Skouta, R., Zaitsev, E. M., Gleason, C. E., Patel, D. N., Bauer, A. J., Cantley, A. M., Yang, W. S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.042 · Cited by 18,691 · see citing works
Regulation of Ferroptotic Cancer Cell Death by GPX4
Yang, W. S., SriRamaratnam, R., Welsch, M. E., Shimada, K., Skouta, R., Viswanathan, V. S., Cheah, J. H., Clemons, P. A., Shamji, A. F., Clish, C. B., et al. (2014) · Cell · doi:10.1016/j.cell.2013.12.010 · Cited by 7,713 · see citing works
Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial.
Burris, H. A., Moore, M. J., Andersen, J., Green, M. R., Rothenberg, M. L., Modiano, M., Cripps, M. C., Portenoy, R. K., Storniolo, A. M., Tarassoff, P. G., et al. (1997) · Journal of Clinical Oncology · doi:10.1200/jco.1997.15.6.2403 · Cited by 5,895 · see citing works
Clonogenic assay of cells in vitro
Franken, N. A. P., Rodermond, H. M., Stap, J., HAVEMAN, J., & Chris van, B. R. E. E. (2006) · Nature Protocols · doi:10.1038/nprot.2006.339 · Cited by 4,202 · see citing works
An Nrf2/Small Maf Heterodimer Mediates the Induction of Phase II Detoxifying Enzyme Genes through Antioxidant Response Elements
Itoh, K., Chiba, T., Takahashi, S., Ishii, T., Igarashi, K., Katoh, Y., Oyake, T., Hayashi, N., Satoh, K., Hatayama, I., et al. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6943 · Cited by 3,999 · see citing works
Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
Jones, S., Zhang, X., Parsons, D. W., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., et al. (2008) · Science · doi:10.1126/science.1164368 · Cited by 3,969 · see citing works
Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice
Friedmann Angeli, J. P., Schneider, M., Proneth, B., Tyurina, Y. Y., Tyurin, V. A., Hammond, V. J., Herbach, N., Aichler, M., Walch, A., Eggenhofer, E., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb3064 · Cited by 3,732 · see citing works
Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury
Degterev, A., Huang, Z., Boyce, M., Li, Y., Jagtap, P., Mizushima, N., Cuny, G. D., Mitchison, T. J., Moskowitz, M. A., & Yuan, J. (2005) · Nature Chemical Biology · doi:10.1038/nchembio711 · Cited by 3,068 · see citing works
Mitochondria and cell death: outer membrane permeabilization and beyond
Tait, S. W. G., & Green, D. R. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2952 · Cited by 2,593 · see citing works
Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis
DeNicola, G. M., Karreth, F. A., Humpton, T. J., Gopinathan, A., Wei, C., Frese, K., Mangal, D., Yu, K. H., Yeo, C. J., Calhoun, E. S., et al. (2011) · Nature · doi:10.1038/nature10189 · Cited by 2,277 · see citing works
Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes
Almoguera, C., Shibata, D. K., Forrester, K., Wj, M., Arnheim, N., & Perucho, M. (1988) · Cell · doi:10.1016/0092-8674(88)90571-5 · Cited by 2,100 · see citing works
Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis
Dixon, S. J., Patel, D. N., Welsch, M., Skouta, R., Lee, E. D., Hayano, M., Thomas, A. G., Gleason, C. E., Tatonetti, N. P., Slusher, B. S., et al. (2014) · eLife · doi:10.7554/elife.02523 · Cited by 2,088 · see citing works
Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism
Ying, H., Kimmelman, A. C., Lyssiotis, C. A., Hua, S., Chu, G. C., Fletcher-Sananikone, E., Locasale, J. W., Son, J., Zhang, H., Coloff, J. L., et al. (2012) · Cell · doi:10.1016/j.cell.2012.01.058 · Cited by 2,043 · see citing works
Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway
Son, J., Lyssiotis, C. A., Ying, H., Wang, X., Hua, S., Ligorio, M., Perera, R. M., Ferrone, C. R., Mullarky, E., Shyh-Chang, N., et al. (2013) · Nature · doi:10.1038/nature12040 · Cited by 1,990 · see citing works
Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells.
Yang, W. S., & Stockwell, B. R. (2008) · Chemistry & Biology · doi:10.1016/j.chembiol.2008.02.010 · Cited by 1,876 · see citing works
Ferrostatins Inhibit Oxidative Lipid Damage and Cell Death in Diverse Disease Models
Skouta, R., Dixon, S. J., Wang, J., Dunn, D. E., Orman, M., Shimada, K., Rosenberg, P. A., Lo, D. C., Weinberg, J. M., Linkermann, A., et al. (2014) · Journal of the American Chemical Society · doi:10.1021/ja411006a · Cited by 1,146 · cited 1× · see citing works
“We therefore asked if Fer-1 might act via blocking of localized ROS production in ART-treated Panc-1 cells, as Fer-1 was shown to inhibit lipid peroxidation during ferroptotic cell death [28, 47, 48].”
Background
Ferritin: a cytoprotective antioxidant strategem of endothelium.
Balla, G., Jacob, H., Balla, J., Rosenberg, M. E., Nath, K. A., Apple, F., Eaton, J. W., & Vercellotti, G. M. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)37165-0 · Cited by 1,097 · see citing works
Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial.
(2005) · The Lancet · doi:10.1016/s0140-6736(05)67176-0 · Cited by 1,050 · see citing works
Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial
Dondorp, A. M., Fanello, C. A., Hendriksen, I. C. E., Gomes, E., Seni, A., Chhaganlal, K. D., Bojang, K., Olaosebikan, R., Anunobi, N., Maitland, K., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)61924-1 · Cited by 1,015 · see citing works
KRAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas
Smit, V. T. H. B. M., Boot, A. J., de Vries-Smits, A. M. M., Fleuren, G. J., Cornelisse, C. J., & Bos, J. L. (1988) · Nucleic Acids Research · doi:10.1093/nar/16.16.7773 · Cited by 625 · see citing works
C11-BODIPY581/591, an oxidation-sensitive fluorescent lipid peroxidation probe: (micro)spectroscopic characterization and validation of methodology
Drummen, G. P. C., van Liebergen, L. C. M., Op den Kamp, J. A. F., & Post, J. A. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00848-1 · Cited by 594 · see citing works
Pretreatment Mitochondrial Priming Correlates with Clinical Response to Cytotoxic Chemotherapy
Chonghaile, T. N., Sarosiek, K. A., Vo, T.-T. T., Ryan, J. A., Tammareddi, A., Moore, V. D. G., Deng, J., Anderson, K. C., Richardson, P. G. G., Tai, Y., et al. (2011) · Science · doi:10.1126/science.1206727 · Cited by 588 · see citing works
Combined gene expression analysis of whole-tissue and microdissected pancreatic ductal adenocarcinoma identifies genes specifically overexpressed in tumor epithelia.
Badea, L., Herlea, V., Dima, S., Dumitraşcu, T., & Popescu, I. (2008) · PubMed · Cited by 531 · see citing works
Transferrin receptors in human tissues: their distribution and possible clinical relevance.
Gatter, K. C., Brown, G., Trowbridge, I. S., Woolston, R.-E., & Mason, D. Y. (1983) · Journal of Clinical Pathology · doi:10.1136/jcp.36.5.539 · Cited by 530 · see citing works
Oncogenic KRAS signalling in pancreatic cancer
Eser, S., Schnieke, A., Schneider, G., & Saur, D. (2014) · British Journal of Cancer · doi:10.1038/bjc.2014.215 · Cited by 504 · see citing works
Necrostatin-1 analogues: critical issues on the specificity, activity and in vivo use in experimental disease models
Takahashi, N., Duprez, L., Grootjans, S., Cauwels, A., Nerinckx, W., DuHadaway, J. B., Goossens, V, Roelandt, R., Van Hauwermeiren, F., Libert, C., et al. (2012) · Cell Death & Disease · doi:10.1038/cddis.2012.176 · Cited by 465 · see citing works
Whole-exome sequencing uncovers frequent GNAS mutations in intraductal papillary mucinous neoplasms of the pancreas
Furukawa, T., Kuboki, Y., Tanji, E., Yoshida, S., Hatori, T., Yamamoto, M., Shibata, N., Shimizu, K., Kamatani, N., & Shiratori, K. (2011) · Scientific Reports · doi:10.1038/srep00161 · Cited by 442 · see citing works
Abnormal Glucose Metabolism and Pancreatic Cancer Mortality
Gapstur, S. M. (2000) · JAMA · doi:10.1001/jama.283.19.2552 · Cited by 420 · see citing works
Sorafenib induces ferroptosis in human cancer cell lines originating from different solid tumors.
Lachaier, E., Louandre, C., Godin, C., Saidak, Z., Baert, M., Diouf, M., Chauffert, B., & Galmiche, A. (2014) · PubMed · Cited by 396 · see citing works
European cancer mortality predictions for the year 2014
Malvezzi, M., Bertuccio, P., Levi, F., Vecchia, C. L., & Negri, E. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu138 · Cited by 380 · see citing works
The retinoblastoma (Rb) protein regulates ferroptosis induced by sorafenib in human hepatocellular carcinoma cells
Louandre, C., Marcq, I., Bouhlal, H., Lachaier, E., Godin, C., Saidak, Z., François, C., Chatelain, D., Debuysscher, V., Barbare, J.-C., et al. (2015) · Cancer Letters · doi:10.1016/j.canlet.2014.11.014 · Cited by 374 · see citing works
Selective toxicity of dihydroartemisinin and holotransferrin toward human breast cancer cells
Singh, N. P., & Lai, H. C. (2001) · Life Sciences · doi:10.1016/s0024-3205(01)01372-8 · Cited by 321 · see citing works
Immortal Human Pancreatic Duct Epithelial Cell Lines with Near Normal Genotype and Phenotype
Ouyang, H. W., Mou, L.-J., Luk, C. K., Liu, N., Karásková, J., Squire, J. A., & Tsao, M. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64800-6 · Cited by 316 · see citing works
Lysosomes in iron metabolism, ageing and apoptosis
Kurz, T., Terman, A., Gustafsson, B., & Brunk, U. T. (2008) · Histochemistry and Cell Biology · doi:10.1007/s00418-008-0394-y · Cited by 302 · see citing works
Enhancement of cytotoxicity of artemisinins toward cancer cells by ferrous iron
Efferth, T., Benakis, A., Romero, M. R., Tomicic, M., Rauh, R., Steinbach, D., Häfer, R., Stamminger, T., Oesch, F., Kaina, B., et al. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.06.023 · Cited by 266 · see citing works
Anti–Tumor Necrosis Factor Therapy Inhibits Pancreatic Tumor Growth and Metastasis
Egberts, J. D., Cloosters, V., Noack, A., Schniewind, B., Thon, L., Klose, S., Kettler, B., von Forstner, C., Kneitz, C., Tepel, J., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5704 · Cited by 259 · see citing works
Artesunate Induces ROS-Mediated Apoptosis in Doxorubicin-Resistant T Leukemia Cells
Efferth, T., Giaisi, M., Merling, A., Krammer, P. H., & Li‐Weber, M. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000693 · Cited by 256 · see citing works
Review of the clinical pharmacokinetics of artesunate and its active metabolite dihydroartemisinin following intravenous, intramuscular, oral or rectal administration
Morris, C. A., Duparc, S., Borghini-Fuhrer, I., Jung, D. T., Shin, C.-S., & Fleckenstein, L. L. (2011) · Malaria Journal · doi:10.1186/1475-2875-10-263 · Cited by 237 · see citing works
Artesunate Activates Mitochondrial Apoptosis in Breast Cancer Cells via Iron-catalyzed Lysosomal Reactive Oxygen Species Production
Hamacher‐Brady, A., Stein, H., Turschner, S., Toegel, I., Mora-Rodríguez, R. A., Jennewein, N., Efferth, T., Eils, R., & Brady, N. R. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.210047 · Cited by 230 · see citing works
Self-citation
Selective killing of K-ras mutant cancer cells by small molecule inducers of oxidative stress
Shaw, A. T., Winslow, M. M., Magendantz, M., Ouyang, C., Dowdle, J. A., Subramanian, A., Lewis, T. A., Maglathin, R. L., Tolliday, N. J., & Jacks, T. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1105941108 · Cited by 229 · see citing works
The xc− cystine/glutamate antiporter: a mediator of pancreatic cancer growth with a role in drug resistance
Lo, M., Ling, V. W. T., Wang, Y. Z., & Gout, P. W. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604485 · Cited by 222 · see citing works
Transferrin receptor is a marker of malignant phenotype in human pancreatic cancer and in neuroendocrine carcinoma of the pancreas
Ryschich, E., Huszty, G., Knaebel, H. P., Härtel, M., Büchler, M. W., & Schmidt, J. (2004) · European Journal of Cancer · doi:10.1016/j.ejca.2004.01.036 · Cited by 199 · see citing works
Artesunate Induces Oxidative DNA Damage, Sustained DNA Double-Strand Breaks, and the ATM/ATR Damage Response in Cancer Cells
Berdelle, N., Nikolova, T., Quiros, S., Efferth, T., & Kaina, B. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0534 · Cited by 181 · see citing works
Artesunate Induces Cell Death in Human Cancer Cells via Enhancing Lysosomal Function and Lysosomal Degradation of Ferritin
Yang, N., Tan, S.-H., Ng, S., Shi, Y. P., Zhou, J., Tan, K. S. W., Wong, W. S. F., & Shen, H. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.564567 · Cited by 175 · see citing works
Artesunate induces oncosis-like cell death in vitro and has antitumor activity against pancreatic cancer xenografts in vivo
Du, J., Zhang, H., Ma, Z.-J., & Ji, K. (2009) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-009-1095-5 · Cited by 159 · see citing works
Lysosomal disruption preferentially targets acute myeloid leukemia cells and progenitors
Sukhai, M. A., Prabha, S., Hurren, R., Rutledge, A. C., Lee, A. Y., Sriskanthadevan, S., Sun, H., Wang, X., Škrtić, M., Seneviratne, A. K., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci64180 · Cited by 149 · see citing works
Visualization of caspase-3-like activity in cells using a genetically encoded fluorescent biosensor activated by protein cleavage
Zhang, J., Wang, X., Cui, W., Wang, W., Zhang, H., Liu, L., Zhang, Z., Li, Z., Ying, G., Zhang, N., et al. (2013) · Nature Communications · doi:10.1038/ncomms3157 · Cited by 144 · see citing works
Targeting apoptosis pathways in pancreatic cancer
Arlt, A., Müerköster, S. S., & Schäfer, H. (2010) · Cancer Letters · doi:10.1016/j.canlet.2010.10.015 · Cited by 143 · see citing works
Mutant KRAS in the initiation of pancreatic cancer
Deramaudt, T. B., & Rustgi, A. K. (2005) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2005.08.003 · Cited by 124 · see citing works
Cellular Uptake and Release of Two Contrasting Iron Chelators
Cable, H. C., & Lloyd, J. B. (1999) · Journal of Pharmacy and Pharmacology · doi:10.1211/0022357991772231 · Cited by 102 · see citing works
Artesunate induces apoptosis via a Bak‐mediated caspase‐independent intrinsic pathway in human lung adenocarcinoma cells
Zhou, C.-J., Pan, W., Wang, X., & Chen, T. S. (2012) · Journal of Cellular Physiology · doi:10.1002/jcp.24086 · Cited by 86 · see citing works
Analysis of genomic DNA alterations and mRNA expression patterns in a panel of human pancreatic cancer cell lines
Gysin, S., Rickert, P., Kastury, K., & McMahon, M. (2005) · Genes Chromosomes and Cancer · doi:10.1002/gcc.20216 · Cited by 70 · see citing works
Combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and actinomycin D induces apoptosis even in TRAIL-resistant human pancreatic cancer cells.
Matsuzaki, H., Schmied, B. M., Ulrich, A. B., Standop, J., Schneider, M. B., Batra, S. K., Picha, K. S., & Pour, P. M. (2001) · PubMed · Cited by 67 · see citing works
Population pharmacokinetics of artesunate and dihydroartemisinin during long-term oral administration of artesunate to patients with metastatic breast cancer
Ericsson, T., Blank, A., von Hagens, C., Ashton, M., & Äbelö, A. (2014) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-014-1754-2 · Cited by 62 · see citing works
Artesunate induces necrotic cell death in schwannoma cells
Button, R. W., Lin, F., Ercolano, E., Vincent, J. H., Hu, B., Hanemann, C. O., & Luo, S. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.434 · Cited by 57 · see citing works
CD95 promotes metastatic spread via Sck in pancreatic ductal adenocarcinoma
Teodorczyk, M., Kleber, S., Wollny, D., Sefrin, J. P., Aykut, B., Mateos, Á., Herhaus, P., Sancho-Martinez, I., Hill, O., Gieffers, C., et al. (2015) · Cell Death and Differentiation · doi:10.1038/cdd.2014.217 · Cited by 55 · see citing works
Identifying pancreatic cancer patients for targeted treatment: the challenges and limitations of the current selection process and vision for the future
Showalter, S. L., Charles, S., Belin, J., Cozzitorto, J. A., Einstein, P., Richards, N. G., Sauter, P. K., Kennedy, E. P., Witkiewicz, A., Brody, J. R., et al. (2010) · Expert Opinion on Drug Delivery · doi:10.1517/17425240903544462 · Cited by 15 · see citing works
Inhibition of hydroxyl radical-induced protein damages by trolox.
Miura, T., Muraoka, S., & Ogiso, T. (1993) · PubMed · Cited by 14 · see citing works

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Stockwell, B. R., Friedmann Angeli, J. P., Bayir, H., Bush, A. I., Conrad, M., Dixon, S. J., Fulda, S., Gascón, S., Hatzios, S. K., Kagan, V. E., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.021 · Cited by 7,695 · see citing works
Ferroptosis: past, present and future
Li, J., Cao, F., Yin, H.-L., Huang, Z.-J., Lin, Z.-T., Mao, N., Sun, B., & Wang, G. (2020) · Cell Death & Disease · doi:10.1038/s41419-020-2298-2 · Cited by 4,171 · see citing works
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Xie, Y., Hou, W., Song, X., Yu, Y., Huang, J., Sun, X., Kang, R., & Tang, D. (2016) · Cell Death & Differentiation · doi:10.1038/cdd.2015.158 · Cited by 3,727 · see citing works
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Yang, W. S., & Stockwell, B. R. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.10.014 · Cited by 3,088 · see citing works
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Chen, X., Kang, R., Kroemer, G., & Tang, D. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-00462-0 · Cited by 2,938 · see citing works
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Hassannia, B., Vandenabeele, P., & Berghe, T. V. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.04.002 · Cited by 2,483 · see citing works
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Chen, X., Li, J., Kang, R., Klionsky, D. J., & Tang, D. (2021) · Autophagy · doi:10.1080/15548627.2020.1810918 · Cited by 2,099 · see citing works
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Mou, Y., Wang, J., Wu, J., He, D., Zhang, C., Duan, C., & Li, B. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0720-y · Cited by 1,943 · see citing works
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Liang, C., Zhang, X., Yang, M., & Dong, X. (2019) · Advanced Materials · doi:10.1002/adma.201904197 · Cited by 1,569 · see citing works
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Seibt, T. M., Proneth, B., & Conrad, M. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.09.014 · Cited by 1,520 · see citing works
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Cao, J. Y., & Dixon, S. J. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2194-1 · Cited by 1,515 · see citing works
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Zheng, J., & Conrad, M. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.10.011 · Cited by 1,338 · see citing works
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Yuan, H., Li, X., Zhang, X., Kang, R., & Tang, D. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.08.124 · Cited by 1,071 · see citing works
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Zhou, B., Liu, J., Kang, R., Klionsky, D. J., Kroemer, G., & Tang, D. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.03.002 · Cited by 1,071 · see citing works
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Gao, W., Wang, Y., Zhou, Y., Wang, X., & Yu, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01046-3 · Cited by 1,069 · see citing works
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The Tumor Suppressor p53 Limits Ferroptosis by Blocking DPP4 Activity
Xie, Y., Zhu, S., Song, X., Sun, X., Fan, Y., Liu, J., Zhong, M., Yuan, H., Zhang, L., Billiar, T. R., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.07.055 · Cited by 952 · see citing works
Reactive oxygen species and cancer paradox: To promote or to suppress?
Galadari, S., Rahman, A. U., Pallichankandy, S., & Thayyullathil, F. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.01.004 · Cited by 895 · see citing works
Targeting cell death pathways for cancer therapy: recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research
Tong, X., Tang, R., Xiao, M., Xu, J., Wang, W., Zhang, B., Liu, J., Yu, X., & Shi, S. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01392-3 · Cited by 883 · see citing works
Regulated cell death (RCD) in cancer: key pathways and targeted therapies
Peng, F., Liao, M., Qin, R., Zhu, S., Peng, C. Y., Fu, L., Chen, Y., & Han, B. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01110-y · Cited by 850 · see citing works
The emerging role of ferroptosis in inflammation
Sun, Y., Chen, P., Zhai, B., Zhang, M., Xiang, Y., Fang, J., Xu, S., Gao, Y., Chen, X., Sui, X., et al. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110108 · Cited by 739 · see citing works
Emerging Strategies of Cancer Therapy Based on Ferroptosis
Shen, Z., Song, J., Yung, B. C., Zhou, Z., Wu, A., & Chen, X. S. (2018) · Advanced Materials · doi:10.1002/adma.201704007 · Cited by 740 · see citing works
RSL3 Drives Ferroptosis Through GPX4 Inactivation and ROS Production in Colorectal Cancer
Sui, X., Zhang, R., Liu, S., Duan, T., Zhai, L., Zhang, M., Han, X., Xiang, Y., Huang, X., Lin, H., et al. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01371 · Cited by 703 · see citing works
Ferroptosis, a new form of cell death, and its relationships with tumourous diseases
Yu, H., Guo, P., Xie, X., Wang, Y., & Chen, G. (2016) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13008 · Cited by 712 · see citing works
The interaction between ferroptosis and lipid metabolism in cancer
Li, D., & Li, Y. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00216-5 · Cited by 713 · see citing works
Nrf2 inhibition reverses the resistance of cisplatin-resistant head and neck cancer cells to artesunate-induced ferroptosis
Roh, J.-L., Kim, E. H., Jang, H., & Shin, D. (2017) · Redox Biology · doi:10.1016/j.redox.2016.12.010 · Cited by 662 · see citing works
Ferroptosis in cancer and cancer immunotherapy
Zhao, L., Zhou, X., Xie, F., Zhang, L., Yan, H., Huang, J., Zhang, C., Zhou, F., Chen, J., & Zhang, L. (2022) · Cancer Communications · doi:10.1002/cac2.12250 · Cited by 684 · see citing works
Molecular mechanisms of ferroptosis and its role in cancer therapy
Xu, T., Ding, W., Ji, X., Ao, X., Liu, Y., Yu, W., & Wang, J. (2019) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14511 · Cited by 639 · see citing works
From ancient herb to modern drug: Artemisia annua and artemisinin for cancer therapy
Efferth, T. (2017) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.02.009 · Cited by 632 · see citing works
Ferroptosis, a novel pharmacological mechanism of anti-cancer drugs
Su, Y., Zhao, B., Zhou, L., Zhang, Z., Shen, Y., Lv, H., AlQudsy, L. H. H., & Shang, P. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.02.015 · Cited by 580 · see citing works
Ferroptosis and Cancer: Mitochondria Meet the “Iron Maiden” Cell Death
Battaglia, A. M., Chirillo, R., Aversa, I., Sacco, A., Costanzo, F. S., & Biamonte, F. (2020) · Cells · doi:10.3390/cells9061505 · Cited by 574 · see citing works
Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine
Luo, H., Vong, C. T., Chen, H., Gao, Y., Lyu, P., Qiu, L., Zhao, M., Liu, Q., Cheng, Z., Zou, J., et al. (2019) · Chinese Medicine · doi:10.1186/s13020-019-0270-9 · Cited by 569 · see citing works
Iron and cancer: recent insights
Manz, D. H., Blanchette, N. L., Paul, B. T., Torti, F. M., & Torti, S. V. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13008 · Cited by 507 · see citing works
Mechanisms of Ferroptosis and Relations With Regulated Cell Death: A Review
Lei, P., Bai, T., & Sun, Y. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00139 · Cited by 535 · see citing works
Inhibition of ferroptosis alleviates atherosclerosis through attenuating lipid peroxidation and endothelial dysfunction in mouse aortic endothelial cell
Bai, T., Li, M., Liu, Y., Qiao, Z., & Wang, Z. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.07.026 · Cited by 534 · see citing works
Ferroptosis and Its Role in Diverse Brain Diseases
Weiland, A., Wang, Y., Wu, W., Lan, X., Han, X., Li, Q., & Wang, J. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1403-3 · Cited by 469 · see citing works
The multifaceted role of reactive oxygen species in tumorigenesis
Kirtonia, A., Sethi, G., & Garg, M. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03536-5 · Cited by 452 · see citing works
The Role of Ferroptosis in Cancer Development and Treatment Response
Lu, B., Chen, X. B., Ying, M. D., He, Q. J., Cao, J., & Yang, B. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00992 · Cited by 444 · see citing works
Breakdown of an Ironclad Defense System: The Critical Role of NRF2 in Mediating Ferroptosis
Anandhan, A., Dodson, M. B., Schmidlin, C. J., Liu, P., & Zhang, D. D. (2020) · Cell chemical biology · doi:10.1016/j.chembiol.2020.03.011 · Cited by 439 · see citing works
Iron and Cancer
Torti, S. V., Manz, D. H., Paul, B. T., Blanchette-Farra, N., & Torti, F. M. (2018) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-082117-051732 · Cited by 426 · see citing works
Identification of essential sites of lipid peroxidation in ferroptosis
von Krusenstiern, A. N., Robson, R. N., Qian, N., Qiu, B., Hu, F., Reznik, E., Smith, N., Zandkarimi, F., Estes, V. M., Dupont, M. M., et al. (2023) · Nature Chemical Biology · doi:10.1038/s41589-022-01249-3 · Cited by 424 · see citing works
The role of NCOA4-mediated ferritinophagy in health and disease
Santana-Codina, N., & Mancias, J. D. (2018) · Pharmaceuticals · doi:10.3390/ph11040114 · Cited by 410 · see citing works
Ferroptosis in Cancer Cell Biology
Bebber, C. M., Müller, F., Clemente, L. P., Weber, J., & von Karstedt, S. (2020) · Cancers · doi:10.3390/cancers12010164 · Cited by 360 · see citing works
Cell death in pancreatic cancer: from pathogenesis to therapy
Chen, X., Zeh, H. J., Kang, R., Kroemer, G., & Tang, D. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00486-6 · Cited by 338 · see citing works
Characterization of ferroptosis in kidney tubular cell death under diabetic conditions
Kim, S., Kang, S., Joo, J., Han, S. H., Shin, H., Nam, B. Y., Park, J., Yoo, T., Kim, G., Lee, P., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03452-x · Cited by 331 · see citing works
Artesunate synergizes with sorafenib to induce ferroptosis in hepatocellular carcinoma
Li, Z., Dai, H.-Q., Huang, X., Ji, F., Deng, J.-H., Wang, Z.-X., Yang, X., Liu, Y., Wu, Y., Chen, P.-H., et al. (2020) · Acta Pharmacologica Sinica · doi:10.1038/s41401-020-0478-3 · Cited by 317 · see citing works
Emerging mechanisms and targeted therapy of ferroptosis in cancer
Wang, H., Cheng, Y., Mao, C., Liu, S., Xiao, D., Huang, J. X., & Tao, Y. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.03.022 · Cited by 320 · see citing works
Cysteine Dioxygenase 1 Mediates Erastin-Induced Ferroptosis in Human Gastric Cancer Cells
Hao, S., Jiang, Y., He, W., Huang, Q., Zhao, Y., Liang, B., Zhang, S., Wen, Z., Dong, S., Rao, J., et al. (2017) · Neoplasia · doi:10.1016/j.neo.2017.10.005 · Cited by 308 · see citing works
The Protective Role of Mitochondrial Ferritin on Erastin-Induced Ferroptosis
Wang, Y., Chang, S.-Y., Wu, Q., Gou, Y.-J., Jia, L., Cui, Y.-M., Yu, P., Shi, Z.-H., Wu, W.-S., Gao, G., et al. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00308 · Cited by 309 · see citing works
A guideline on the molecular ecosystem regulating ferroptosis
Dai, E., Chen, X., Linkermann, A., Jiang, X., Kang, R., Kagan, V. E., Bayır, H., Yang, W. S., García‐Sáez, A. J., Ioannou, M. S., et al. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01360-8 · Cited by 308 · see citing works
Dihydroartemisinin (DHA) induces ferroptosis and causes cell cycle arrest in head and neck carcinoma cells
Lin, R., Zhang, Z., Chen, L., Zhou, Y., Zou, P., Feng, C., Wang, L., & Liang, G. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.07.033 · Cited by 296 · see citing works
Ferritinophagy/ferroptosis: Iron‐related newcomers in human diseases
Tang, M., Chen, Z., Wu, D., & Chen, L. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.26954 · Cited by 290 · see citing works
Ferroptosis and Its Potential Role in Human Diseases
Han, C., Liu, Y., Dai, R., Ismail, N., Su, W., & Li, B. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00239 · Cited by 274 · see citing works
The induction of ferroptosis by impairing STAT3/Nrf2/GPx4 signaling enhances the sensitivity of osteosarcoma cells to cisplatin
Liu, Q., & Wang, K. (2019) · Cell Biology International · doi:10.1002/cbin.11121 · Cited by 274 · see citing works
The function and mechanism of ferroptosis in cancer
Wang, Y., Wei, Z., Pan, K., Li, J., & Chen, Q. (2020) · APOPTOSIS · doi:10.1007/s10495-020-01638-w · Cited by 262 · see citing works
PDK4 dictates metabolic resistance to ferroptosis by suppressing pyruvate oxidation and fatty acid synthesis
Song, X., Liu, J., Kuang, F., Chen, X., Zeh, H. J., Kang, R., Kroemer, G., Xie, Y., & Tang, D. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.108767 · Cited by 258 · see citing works
Identification of baicalein as a ferroptosis inhibitor by natural product library screening
Xie, Y., Song, X., Sun, X., Huang, J. L., Zhong, M., Lotze, M. T., Zeh, H. J., Kang, R., & Tang, D. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.03.052 · Cited by 246 · see citing works
Artemisinin as an anticancer drug: Recent advances in target profiling and mechanisms of action
Wong, Y. K., Xu, C., Kalesh, K., He, Y., Lin, Q., Wong, W. S. F., Shen, H., & Wang, J. (2017) · Medicinal Research Reviews · doi:10.1002/med.21446 · Cited by 241 · see citing works
Role of ferroptosis in hepatocellular carcinoma
Nie, J., Lin, B., Zhou, M., Wu, L. J., & Zheng, T. (2018) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-018-2740-3 · Cited by 234 · see citing works
Systematic Analysis of the Aberrances and Functional Implications of Ferroptosis in Cancer
Liu, Z., Zhao, Q., Zuo, Z.-X., Yu, K., Yu, K., Zhang, X.-L., Zhang, X., Sheng, H., Ju, H., Cheng, H., et al. (2020) · iScience · doi:10.1016/j.isci.2020.101302 · Cited by 222 · see citing works
Artemisinin, the Magic Drug Discovered from Traditional Chinese Medicine
Wang, J., Xu, C., Wong, Y. K., Li, Y., Liao, F., Jiang, T., & Tu, Y. (2018) · Engineering · doi:10.1016/j.eng.2018.11.011 · Cited by 217 · see citing works
Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy
Huang, R., Chen, H., Liang, J., Li, Y., Yang, J., Luo, C., Tang, Y., Ding, Y., Liu, X., Yuan, Q., et al. (2021) · Journal of Cancer · doi:10.7150/jca.54699 · Cited by 218 · see citing works
Iron and copper: critical executioners of ferroptosis, cuproptosis and other forms of cell death
Li, Y., Du, Y., Zhou, Y., Chen, Q., Luo, Z., Ren, Y., Chen, X., & Chen, G. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01267-1 · Cited by 220 · see citing works
Pseudolaric acid B triggers ferroptosis in glioma cells via activation of Nox4 and inhibition of xCT
Wang, Z., Ding, Y., Wang, X., Lu, S., Wang, C., He, C. H., Wang, L., Piao, M., Chi, G., Luo, Y., et al. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.04.021 · Cited by 211 · see citing works
Artesunate activates the ATF4-CHOP-CHAC1 pathway and affects ferroptosis in Burkitt's Lymphoma
Wang, N., Zeng, G., Yin, J.-L., & Bian, Z. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.09.023 · Cited by 207 · see citing works
Ferroptosis: Opportunities and Challenges in Myocardial Ischemia‐Reperfusion Injury
Zhao, W., Zhou, Y., Xu, T., & Wu, Q. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/9929687 · Cited by 212 · see citing works
Targeting ferroptosis in breast cancer
Li, Z., Chen, L., Chen, C., Zhou, Y., Hu, D., Yang, J., Chen, Y., Zhuo, W., Mao, M., Zhang, X., et al. (2020) · Biomarker Research · doi:10.1186/s40364-020-00230-3 · Cited by 203 · see citing works
TMEM164 is a new determinant of autophagy-dependent ferroptosis
Liu, J., Liu, Y., Wang, Y., Li, C., Xie, Y., Klionsky, D. J., Kang, R., & Tang, D. (2022) · Autophagy · doi:10.1080/15548627.2022.2111635 · Cited by 191 · see citing works
Five-Membered Ring Peroxide Selectively Initiates Ferroptosis in Cancer Cells
Abrams, R. P. M., Carroll, W. L., & Woerpel, K. A. (2016) · ACS Chemical Biology · doi:10.1021/acschembio.5b00900 · Cited by 189 · see citing works
Contribution of reactive oxygen species to ovarian cancer cell growth arrest and killing by the anti-malarial drug artesunate
Greenshields, A. L., Shepherd, T. G., & Hoskin, D. W. (2016) · Molecular Carcinogenesis · doi:10.1002/mc.22474 · Cited by 189 · see citing works
Autophagy and Ferroptosis—What Is the Connection?
Kang, R., & Tang, D. (2017) · Current Pathobiology Reports · doi:10.1007/s40139-017-0139-5 · Cited by 185 · see citing works
Nanomaterial-induced ferroptosis for cancer specific therapy
Liu, M., Liu, B., Liu, Q., Du, K., Wang, Z., & He, N. (2019) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2018.12.015 · Cited by 180 · see citing works
Ferroptosis and ferritinophagy in diabetes complications
He, J., Li, Z., Xia, P., Shi, A., FuChen, X., Zhang, J., & Yu, P. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101470 · Cited by 181 · see citing works
Emerging agents that target signaling pathways in cancer stem cells
Yang, Y., Li, X., Wang, T., Guo, Q., Xi, T., & Zheng, L. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00901-6 · Cited by 177 · see citing works
Targeting de novo lipogenesis and the Lands cycle induces ferroptosis in KRAS-mutant lung cancer
Bartolacci, C., Andreani, C., do Vale, G. D., Berto, S., Melegari, M., Crouch, A. C., Baluya, D. L., Kemble, G. W., Hodges, K. B., Starrett, J. H., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31963-4 · Cited by 179 · see citing works
Ferroptosis in Cancer Treatment: Another Way to Rome
Wu, Y., Yu, C., Luo, M., Chen, C., Qiu, J., Zhang, S., & Hu, K. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.571127 · Cited by 175 · see citing works
KLF2 inhibits cancer cell migration and invasion by regulating ferroptosis through GPX4 in clear cell renal cell carcinoma
Lu, Y., Qin, H., Jiang, B., Lu, W., Hao, J., Cao, W., Du, L., Chen, W., Zhao, X., & Guo, H. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.09.014 · Cited by 176 · see citing works
The emerging roles of MAPK-AMPK in ferroptosis regulatory network
Wang, X., Tan, X., Zhang, J., Wu, J., & Shi, H. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01170-9 · Cited by 172 · see citing works
Regulation and function of autophagy in pancreatic cancer
Li, J., Chen, X., Kang, R., Zeh, H. J., Klionsky, D. J., & Tang, D. (2020) · Autophagy · doi:10.1080/15548627.2020.1847462 · Cited by 160 · see citing works
The Relationship between Ferroptosis and Tumors: A Novel Landscape for Therapeutic Approach
Xia, X., Fan, X., Zhao, M., & Zhu, P. (2019) · Current Gene Therapy · doi:10.2174/1566523219666190628152137 · Cited by 159 · see citing works
Golgi stress mediates redox imbalance and ferroptosis in human cells
Alborzinia, H., Ignashkova, T. I., Dejure, F. R., Gendarme, M., Theobald, J., Wölfl, S., Lindemann, R. K., & Reiling, J. H. (2018) · Communications Biology · doi:10.1038/s42003-018-0212-6 · Cited by 159 · see citing works
Targeting STAT3 signaling pathway in cancer by agents derived from Mother Nature
Mohan, C. D., Rangappa, S., Preetham, H. D., Nayaka, S. C., Gupta, V. K., Basappa, B., Sethi, G., & Rangappa, K. S. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.03.016 · Cited by 158 · see citing works
Targeting ferroptosis for cancer therapy: exploring novel strategies from its mechanisms and role in cancers
Jiang, M., Qiao, M., Zhao, C., Deng, J., Li, X., & Zhou, C. (2020) · Translational Lung Cancer Research · doi:10.21037/tlcr-20-341 · Cited by 157 · see citing works
Astragaloside IV regulates the ferroptosis signaling pathway via the Nrf2/SLC7A11/GPX4 axis to inhibit PM2.5-mediated lung injury in mice
Wang, X., Wang, Y., Huang, D., Shi, S., Pei, C., Wu, Y., Shen, Z., Wang, F., & Wang, Z. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.109186 · Cited by 157 · see citing works
Ferroptosis in hepatocellular carcinoma: mechanisms and targeted therapy
Ajoolabady, A., Tang, D., Kroemer, G., & Ren, J. T. (2022) · British Journal of Cancer · doi:10.1038/s41416-022-01998-x · Cited by 154 · see citing works
Iron-based nanoparticles for MR imaging-guided ferroptosis in combination with photodynamic therapy to enhance cancer treatment
Chen, Q., Ma, X., Xie, L., Chen, W., Xu, Z., Song, E., Zhu, X., & Song, Y. (2021) · Nanoscale · doi:10.1039/d0nr08757b · Cited by 150 · see citing works
Ferroptosis-Related Gene Signature Predicts Glioma Cell Death and Glioma Patient Progression
Liu, H.-J., Hu, H., Li, G., Zhang, Y., Wu, F., Liu, X., Wang, K., Zhang, C., & Jiang, T. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00538 · Cited by 146 · see citing works
Redox Paradox: A Novel Approach to Therapeutics-Resistant Cancer
Chaiswing, L., Clair, W. H. S., & Clair, D. K. S. (2018) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7485 · Cited by 147 · see citing works
Targeting ferroptosis in pancreatic cancer: a double-edged sword
Chen, X., Kang, R., Kroemer, G., & Tang, D. (2021) · Trends in cancer · doi:10.1016/j.trecan.2021.04.005 · Cited by 140 · see citing works
Dancing with reactive oxygen species generation and elimination in nanotheranostics for disease treatment
Zhou, Z., Ni, K., Deng, H., & Chen, X. S. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.06.006 · Cited by 139 · see citing works
Revealing the Viscosity Changes in Lipid Droplets during Ferroptosis by the Real-Time and In Situ Near-Infrared Imaging
Dong, B., Song, W., Lu, Y., Sun, Y., & Lin, W. (2020) · ACS Sensors · doi:10.1021/acssensors.0c02015 · Cited by 137 · see citing works
IMCA Induces Ferroptosis Mediated by SLC7A11 through the AMPK/mTOR Pathway in Colorectal Cancer
Zhang, L., Liu, W., Liu, F., Wang, Q., Song, M., Yu, Q., Tang, K., Teng, T., Wu, D., Wang, X.-J., et al. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/1675613 · Cited by 139 · see citing works
Induction and application of ferroptosis in cancer therapy
Nie, Q. H., Hu, Y., Yu, X. H., Li, X., & Fang, X. (2022) · Cancer Cell International · doi:10.1186/s12935-021-02366-0 · Cited by 139 · see citing works
Haloperidol, a sigma receptor 1 antagonist, promotes ferroptosis in hepatocellular carcinoma cells
Bai, T., Wang, S., Zhao, Y., Zhu, R., Wang, W., & Sun, Y. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.07.136 · Cited by 137 · see citing works
Progress in Understanding Ferroptosis and Challenges in Its Targeting for Therapeutic Benefit
Zou, Y., & Schreiber, S. L. (2020) · Cell chemical biology · doi:10.1016/j.chembiol.2020.03.015 · Cited by 130 · see citing works
Ferroptosis: An emerging approach for targeting cancer stem cells and drug resistance
Elgendy, S. M., Alyammahi, S. K., Alhamad, D. W., Abdin, S. M., & Omar, H. A. (2020) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2020.103095 · Cited by 133 · see citing works
Artesunate Inhibits Growth of Sunitinib-Resistant Renal Cell Carcinoma Cells through Cell Cycle Arrest and Induction of Ferroptosis
Markowitsch, S. D., Schupp, P., Lauckner, J., Vakhrusheva, O., Slade, K. S., Mager, R., Efferth, T., Haferkamp, A., & Juengel, E. (2020) · Cancers · doi:10.3390/cancers12113150 · Cited by 129 · see citing works
Novel insights on targeting ferroptosis in cancer therapy
Zuo, S., Yu, J., Pan, H., & Lu, L. (2020) · Biomarker Research · doi:10.1186/s40364-020-00229-w · Cited by 127 · see citing works
Novel insights into ferroptosis: Implications for age-related diseases
Zhou, R., Chen, Y., Wei, X., Yu, B., Xiong, Z., Lu, C., & Hu, W. M. (2020) · Theranostics · doi:10.7150/thno.50663 · Cited by 132 · see citing works
Ferroptotic therapy in cancer: benefits, side effects, and risks
Diao, J., Jia, Y., Dai, E., Liu, J., Kang, R., Tang, D., Han, L., Zhong, Y., & Meng, L. (2024) · Molecular Cancer · doi:10.1186/s12943-024-01999-9 · Cited by 126 · see citing works

Emerging Potential Mechanism and Therapeutic Target of Ferroptosis in PDAC: A Promising Future
Li, C., Yin, X., Liu, Z., & Wang, J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232315031 · Cited by 22 · see citing works
Abstract 5984: Small molecule induced KRAS activation triggers ferroptosis in mutant KRAS expressing PDAC
Zhu, H., Iskandar, K. B., Sulaiman, N. S., Leong, B. J., Pang, H., Carrer, A., Armand, A., Oury, F., & Pervaiz, S. (2026) · Cancer Research · doi:10.1158/1538-7445.am2026-5984
Abstract P87: Drug-induced Hyperactivation of the oncogene KRAS induces ferroptosis in G12-mutant KRAS Pancreatic Ductal Adenocarcinoma (PDAC)
Zhu, H., Iskandar, K. B., Sulaiman, N. S., Joseph, B., Armand, A., Oury, F., & Pervaiz, S. (2026) · Cancer Research · doi:10.1158/1538-7445.fcs2025-p87
Role of GRP78 inhibiting artesunate-induced ferroptosis in KRAS mutant pancreatic cancer cells
Wang, K., Zhang, Z., Wang, M., Cao, X., Qi, J., Wang, D., Gong, A., & Zhu, H. (2019) · Drug Design Development and Therapy · doi:10.2147/dddt.s199459 · Cited by 86 · see citing works
Oncogenic KRAS Promotes Ferroptosis in Pancreatic Cancer Through Regulation of the Fosl1-Tfrc Axis
Zhao, H., Huang, Q., Liu, Y., & Wu, W. (2024) · Pancreas · doi:10.1097/mpa.0000000000002426 · Cited by 7 · see citing works

Authors: Eling, N., Reuter, L., Hazin, J., Hamacher-Brady, A., & Brady, N. R.
Affiliations: German Cancer Research Center (DE)
Lysosomal Systems Biology, German Cancer Research Center (DKFZ), Heidelberg, Germany
ORCID: Eling, Nils
Brady, Nathan R.
Venue: Oncoscience
Publisher: Impact Journals, LLC
Published: 2015-05-02
Volume: 2
Issue: 5
Pages: 517-532
ISSN: 2331-4737 (ISSN-L)
DOI: 10.18632/oncoscience.160
PMC: PMC4468338
OpenAlex: W2418439210
Cited by: 524
References: 59
Citations by year: 2026: 22 · 2025: 41 · 2024: 57 · 2023: 71 · 2022: 92 · 2021: 91 · 2020: 60 · 2019: 26 · 2018: 21 · 2017: 23 · 2016: 15 · 2015: 2 · 2014: 1
FWCI: 16.10
Type: journal article
Language: en
Open access: diamond
doi.org
Licence: cc-by
Locations: Oncoscience (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: Deutsches Krebsforschungszentrum
Bundesministerium für Bildung und Forschung
University of Toronto
Tianjin Medical University
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Keywords: artesunate, ferroptosis, pancreatic ductal adenocarcinoma, reactive oxygen species, lysosomal iron, lipid peroxidation, ferrostatin-1, antioxidant homeostasis, necroptosis, apoptosis resistance, anticancer drug repurposing

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Identification of artesunate as a specific activator of ferroptosis in pancreatic cancer cells

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