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Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism
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The major obstacle in cancer treatment is the resistance of cancer cells to therapies. Nrf2 is a transcription factor that regulates a cellular defense response and is ubiquitously expressed at low basal levels in normal tissues due to Keap1-dependent ubiquitination and proteasomal degradation. Recently, Nrf2 has emerged as an important contributor to chemoresistance. High constitutive expression of Nrf2 was found in many types of cancers, creating an environment conducive for cancer cell survival. Here, we report the identification of brusatol as a unique inhibitor of the Nrf2 pathway that sensitizes a broad spectrum of cancer cells and A549 xenografts to cisplatin and other chemotherapeutic drugs. Mechanistically, brusatol selectively reduces the protein level of Nrf2 through enhanced ubiquitination and degradation of Nrf2. Consequently, expression of Nrf2-downstream genes is reduced and the Nrf2-dependent protective response is suppressed. In A549 xenografts, brusatol and cisplatin cotreatment induced apoptosis, reduced cell proliferation, and inhibited tumor growth more substantially when compared with cisplatin treatment alone. Additionally, A549-K xenografts, in which Nrf2 is expressed at very low levels due to ectopic expression of Keap1, do not respond to brusatol treatment, demonstrating that brusatol-mediated sensitization to cisplatin is Nrf2 dependent. Moreover, a decrease in drug detoxification and impairment in drug removal may be the primary mechanisms by which brusatol enhances the efficacy of chemotherapeutic drugs. Taken together, these results clearly demonstrate the effectiveness of using brusatol to combat chemoresistance and suggest that brusatol can be developed into an adjuvant chemotherapeutic drug.
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“brusatol has been shown to enhance the efficacy of chemotherapy by inhibiting Nrf2 [229,230].”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [229]
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Citations
Cites
Cell Survival Responses to Environmental Stresses Via the Keap1-Nrf2-ARE Pathway
Kensler, T. W., Wakabayashi, N., & Biswal, S. (2007) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.46.120604.141046 · Cited by 3,630
Kobayashi, A., Kang, M.-I., Okawa, H., Ohtsuji, M., Zenke, Y., Chiba, T., Igarashi, K., & Yamamoto, M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.16.7130-7139.2004 · Cited by 2,224
Dinkova-Kostova, A. T., Holtzclaw, W. D., Cole, R. N., Itoh, K., Wakabayashi, N., Katoh, Y., Yamamoto, M., & Talalay, P. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.172398899 · Cited by 1,947
Keap1 Is a Redox-Regulated Substrate Adaptor Protein for a Cul3-Dependent Ubiquitin Ligase Complex
Zhang, D. D., Lo, S., Cross, J. V., Templeton, D. J., & Hannink, M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.24.10941-10953.2004 · Cited by 1,284
Self-citationMechanistic Studies of the Nrf2-Keap1 Signaling Pathway
Zhang, D. D. (2006) · Drug Metabolism Reviews · doi:10.1080/03602530600971974 · Cited by 1,105
Self-citationRamos-Gomez, M., Kwak, M.-K., Dolan, P. M., Itoh, K., Yamamoto, M., Talalay, P., & Kensler, T. W. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.051618798 · Cited by 1,102
Dysfunctional KEAP1–NRF2 Interaction in Non-Small-Cell Lung Cancer
Singh, A., Misra, V., Thimmulappa, R. K., Lee, H., Ames, S., Hoque, M. O., Herman, J. G., Baylin, S. B., Sidransky, D., Gabrielson, E., et al. (2006) · PLoS Medicine · doi:10.1371/journal.pmed.0030420 · Cited by 1,060
Cullinan, S. B., Gordan, J. D., Jin, J., Harper, J. W., & Diehl, J. A. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.19.8477-8486.2004 · Cited by 986
NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer
Hayes, J. D., & McMahon, M. J. (2009) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2008.12.008 · Cited by 870
Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2
Wang, X.-J., Sun, Z., Villeneuve, N. F., Zhang, S., Zhao, F., Li, Y., Chen, W., Yi, X., Zheng, W., Wondrak, G. T., et al. (2008) · Carcinogenesis · doi:10.1093/carcin/bgn095 · Cited by 839
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Sun, X., Ou, Z., Chen, R., Niu, X., Chen, D., Kang, R., & Tang, D. (2016) · Hepatology · doi:10.1002/hep.28251 · Cited by 2,012
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Yamamoto, M., Kensler, T. W., & Motohashi, H. (2018) · Physiological Reviews · doi:10.1152/physrev.00023.2017 · Cited by 1,968
Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases
Cuadrado, A., Rojo, A. I., Wells, G., Hayes, J. D., Cousin, S. P., Rumsey, W. L., Attucks, O. C., Franklin, S., Levonen, A., Kensler, T. W., et al. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-018-0008-x · Cited by 1,510
The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer
Kansanen, E., Kuosmanen, S. M., Leinonen, H., & Levonen, A.-L. (2013) · Redox Biology · doi:10.1016/j.redox.2012.10.001 · Cited by 1,313
The emerging role of the Nrf2–Keap1 signaling pathway in cancerPreprint
Jaramillo, M. C., & Zhang, D. D. (2013) · Genes & Development · doi:10.1101/gad.225680.113 · Cited by 1,326
Self-citationGlutathione metabolism in cancer progression and treatment resistance
Bansal, A., & Simon, M. C. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201804161 · Cited by 1,253
Role of Glutathione in Cancer Progression and Chemoresistance
Traverso, N., Ricciarelli, R., Nitti, M., Marengo, B., Furfaro, A. L., Pronzato, M. A., Marinari, U. M., & Domenicotti, C. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/972913 · Cited by 1,208
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Panieri, E., & Santoro, M. M. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.105 · Cited by 1,187
Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease
Ngo, V., & Duennwald, M. L. (2022) · Antioxidants · doi:10.3390/antiox11122345 · Cited by 1,130
NRF2 and cancer: the good, the bad and the importance of context
Sporn, M. B., & Liby, K. T. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3278 · Cited by 1,067
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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
Shen, D.-W., Pouliot, L. M., Hall, M. D., & Gottesman, M. M. (2012) · Pharmacological Reviews · doi:10.1124/pr.111.005637 · Cited by 955
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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 895
Cragg, G. M. L., & Pezzuto, J. M. (2015) · Medical Principles and Practice · doi:10.1159/000443404 · Cited by 845
The Keap1–Nrf2–ARE Pathway As a Potential Preventive and Therapeutic Target: An Update
Lu, M., Ji, J., Jiang, Z., & You, Q. (2016) · Medicinal Research Reviews · doi:10.1002/med.21396 · Cited by 815
Small Molecule Modulators of Keap1‐ Nrf2‐ ARE Pathway as Potential Preventive and Therapeutic Agents
Magesh, S., Chen, Y., & Hu, L. (2012) · Medicinal Research Reviews · doi:10.1002/med.21257 · Cited by 760
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Vomund, S., Schäfer, A., Parnham, M., Brüne, B., & Von Knethen, A. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18122772 · Cited by 752
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Sun, X., Niu, X., Chen, R., He, W., Chen, D., Kang, R., & Tang, D. (2016) · Hepatology · doi:10.1002/hep.28574 · Cited by 709
Toward clinical application of the Keap1-Nrf2 pathway
Suzuki, T., Motohashi, H., & Yamamoto, M. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.04.005 · Cited by 680
Jordan, E. J., Kim, H. R., Arcila, M. E., Barron, D., Chakravarty, D., Gao, J., Chang, M. T., Ni, A., Kundra, R., Jonsson, P., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-1337 · Cited by 643
p62 links autophagy and Nrf2 signaling
Jiang, T., Harder, B. G., de la Vega, M. R., Wong, P. K., Chapman, E., & Zhang, D. D. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.06.014 · Cited by 657
Self-citationThe Dual Roles of NRF2 in Cancer
Menegon, S., Columbano, A., & Giordano, S. (2016) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2016.05.002 · Cited by 633
Transcription Factor NRF2 as a Therapeutic Target for Chronic Diseases: A Systems Medicine Approach
Cuadrado, A., Manda, G., Hassan, A., Alcaraz, M. J., Barbas, C., Daiber, A., Ghezzi, P., León, R., López, M. G., Oliva, B., et al. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014753 · Cited by 632
Singh, A., Venkannagari, S., Oh, K. H., Zhang, Y., Rohde, J. M., Liu, L., Nimmagadda, S., Sudini, K. R., Brimacombe, K. R., Gajghate, S., et al. (2016) · ACS Chemical Biology · doi:10.1021/acschembio.6b00651 · Cited by 626
Activators and inhibitors of NRF2: a review of their potential for clinical development
Robledinos-Antón, N., Fernández-Ginés, R., Manda, G., & Cuadrado, A. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/9372182 · Cited by 413
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Anandhan, A., Dodson, M. B., Shakya, A., Chen, J., Liu, P., Wei, Y., Tan, H., Wang, Q., Jiang, Z., Yang, K. B., et al. (2023) · Science Advances · doi:10.1126/sciadv.ade9585 · Cited by 531
Self-citationModulating NRF2 in Disease: Timing Is Everything
Dodson, M. B., de la Vega, M. R., Cholanians, A. B., Schmidlin, C. J., Chapman, E., & Zhang, D. D. (2018) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010818-021856 · Cited by 540
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Taguchi, K., & Yamamoto, M. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00085 · Cited by 527
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Rao, S., Tortola, L., Perlot, T., Wirnsberger, G., Novatchkova, M., Nitsch, R., Sykacek, P., Frank, L., Schramek, D., Komnenovic, V., et al. (2014) · Nature Communications · doi:10.1038/ncomms4056 · Cited by 453
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Lei, X. G., Zhu, J., Cheng, W.-H., Bao, Y., Ho, Y.-S., Reddi, A. R., Holmgren, A., & Arnér, E. S. J. (2015) · Physiological Reviews · doi:10.1152/physrev.00010.2014 · Cited by 455
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Koundouros, N., & Poulogiannis, G. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00160 · Cited by 425
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Devarakonda, S. H. K., Morgensztern, D., & Govindan, R. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00077-7 · Cited by 423
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Natural product-derived pharmacological modulators of Nrf2/ARE pathway for chronic diseases
Kumar, H., Kim, I., More, S. V., Kim, B.-W., & Choi, D. (2013) · Natural Product Reports · doi:10.1039/c3np70065h · Cited by 338
Abed, D. A., Goldstein, M., Albanyan, H., Jin, H., & Hu, L. (2015) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2015.05.008 · Cited by 336
NRF2 as a regulator of cell metabolism and inflammation in cancer
He, F., Antonucci, L., & Karin, M. (2020) · Carcinogenesis · doi:10.1093/carcin/bgaa039 · Cited by 332
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Ma, Q., & He, X. (2012) · Pharmacological Reviews · doi:10.1124/pr.110.004333 · Cited by 317
ROS-modulated therapeutic approaches in cancer treatment
Raza, M. H., Siraj, S., Arshad, A., Waheed, U., Aldakheel, F. M., Alduraywish, S. A., & Arshad, M. M. U. D. (2017) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-017-2464-9 · Cited by 304
The KEAP1-NRF2 pathway: Targets for therapy and role in cancer
Adinolfi, S., Patinen, T., Deen, A. J., Pitkänen, S., Härkönen, J., Kansanen, E., Küblbeck, J., & Levonen, A. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102726 · Cited by 326
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Furfaro, A. L., Traverso, N., Domenicotti, C., Piras, S., Moretta, L., Marinari, U. M., Pronzato, M. A., & Nitti, M. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/1958174 · Cited by 303
Oncogenic KRAS Confers Chemoresistance by Upregulating NRF2
Tao, S., Wang, S., Moghaddam, S. J., Ooi, A., Chapman, E., Wong, P. K., & Zhang, D. D. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-1439 · Cited by 291
Self-citationKrajka‐Kuźniak, V., Paluszczak, J., & Baer‐Dubowska, W. (2016) · Pharmacological Reports · doi:10.1016/j.pharep.2016.12.011 · Cited by 288
Ge, M., Tian, H., Mao, L., Li, D., Lin, J., Hu, H., Huang, S., Zhang, C., & Mei, X. (2021) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13657 · Cited by 273
Lin, D., Wang, M., & Koeffler, H. P. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.06.066 · Cited by 249
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Ji, S., Li, Z., Song, W., Wang, Y., Liang, W., Li, K., Tang, S., Wang, Q., Qiao, X., Zhou, D., et al. (2016) · Journal of Natural Products · doi:10.1021/acs.jnatprod.5b00877 · Cited by 242
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Sznarkowska, A., Kostecka, A., Meller, K., & Bielawski, K. P. (2016) · Oncotarget · doi:10.18632/oncotarget.13723 · Cited by 246
Olayanju, A., Copple, I. M., Bryan, H. K., Edge, G. T., Sison, R. L., Wong, M. W., Lai, Z.-Q., Lin, Z.-X., Dunn, K., Sanderson, C. M., et al. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.11.003 · Cited by 232
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Lau, A., Zheng, Y., Tao, S., Wang, H., Whitman, S. A., White, E., & Zhang, D. D. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.01748-12 · Cited by 231
Self-citationMolecular and Chemical Regulation of the Keap1-Nrf2 Signaling Pathway
Keum, Y., & Choi, B. Y. (2014) · Molecules · doi:10.3390/molecules190710074 · Cited by 225
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Bardelčíková, A., Šoltýs, J., & Mojžíš, J. (2023) · Antioxidants · doi:10.3390/antiox12040901 · Cited by 222
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Oncogenic functions of the transcription factor Nrf2
Gañán‐Gómez, I., Wei, Y., Yang, H., Boyano-Adánez, M. C., & Garcia‐Manero, G. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.06.041 · Cited by 203
The KEAP1–NRF2 System as a Molecular Target of Cancer Treatment
Taguchi, K., & Yamamoto, M. (2020) · Cancers · doi:10.3390/cancers13010046 · Cited by 195
“It has been reported that brusatol enhances the efficacy of chemotherapy by inhibiting NRF2 [80] (Figure 4A).”
BackgroundEmerging role of NRF2 in ROS-mediated tumor chemoresistance
Xue, D., Zhou, X., & Qiu, J. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110676 · Cited by 195
Gao, A.-M., Ke, Z., Fang, S., Sun, G., & Chen, H. (2013) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2013.08.008 · Cited by 190
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NRF2: KEAPing Tumors Protected
Pillai, R., Hayashi, M., Zavitsanou, A.-M., & Papagiannakopoulos, T. Y. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0922 · Cited by 196
NRF2 Activation in Cancer: From DNA to Protein
Cloer, E. W., Goldfarb, D., Schrank, T. P., Weissman, B. E., & Major, M. B. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-2723 · Cited by 182
The transcription factor NF‐E2‐related Factor 2 (Nrf2): a protooncogene?
Shelton, P. M., & Jaiswal, A. K. (2012) · The FASEB Journal · doi:10.1096/fj.12-217257 · Cited by 185
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Lee, D., Xu, M., Chiu, D. K., Leibold, J., Tse, A. P., Bao, M. H., Yuen, V. W., Chan, C. Y., Lai, R. K., Chin, D. W., et al. (2018) · Hepatology · doi:10.1002/hep.30467 · Cited by 183
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Copple, I. M. (2012) · Advances in pharmacology · doi:10.1016/b978-0-12-398339-8.00002-1 · Cited by 174
Gounder, S. S., Kannan, S., Devadoss, D., Miller, C. J., Whitehead, K. S., Odelberg, S. J., Firpo, M. A., Paine, R., Hoidal, J. R., Abel, E. D., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045697 · Cited by 173
An update of Nrf2 activators and inhibitors in cancer prevention/promotion
Pouremamali, F., Pouremamali, A., Dadashpour, M., Soozangar, N., & Jeddi, F. (2022) · Cell Communication and Signaling · doi:10.1186/s12964-022-00906-3 · Cited by 183
Harder, B. G., Jiang, T., Wu, T., Tao, S., de la Vega, M. R., Tian, W., Chapman, E., & Zhang, D. D. (2015) · Biochemical Society Transactions · doi:10.1042/bst20150020 · Cited by 171
Self-citationBrucea javanica derived exosome-like nanovesicles deliver miRNAs for cancer therapy
Yan, G., Xiao, Q., Zhao, J., Chen, H., Xu, Y., Tan, M., & Peng, L. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.01.060 · Cited by 174
Gao, A.-M., Ke, Z., Wang, J., Yang, J., Chen, S., & Chen, H. (2013) · Carcinogenesis · doi:10.1093/carcin/bgt108 · Cited by 169
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Torrente, L., & DeNicola, G. M. (2021) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-052220-104025 · Cited by 175
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Tsuchida, K., Tsujita, T., Hayashi, M., Ojima, A., Keleku-Lukwete, N., Katsuoka, F., Otsuki, A., Kikuchi, H., Oshima, Y., Suzuki, M., et al. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.12.041 · Cited by 165
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Zhu, J., Wang, H., Chen, F., Fu, J., Xu, Y., Hou, Y., Kou, H. H., Zhai, C., Nelson, M. B., Zhang, Q., et al. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.09.010 · Cited by 162
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Moon, E. J., & Giaccia, A. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.11.009 · Cited by 160
Bai, X., Chen, Y., Hou, X., Huang, M., & Jin, J. (2016) · Drug Metabolism Reviews · doi:10.1080/03602532.2016.1197239 · Cited by 159
Role of the Keap1–Nrf2 Pathway in Cancer
Leinonen, H. M., Kansanen, E., Pölönen, P., Heinäniemi, M., & Levonen, A. (2014) · Advances in cancer research · doi:10.1016/b978-0-12-420117-0.00008-6 · Cited by 158
Luteolin inhibits the Nrf2 signaling pathway and tumor growth in vivo
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Metadata
- Authors
- Ren, D., Villeneuve, N. F., Jiang, T., Wu, T., Lau, A., Toppin, H. A., & Zhang, D. D.
- Affiliations
- Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ 85721;
- University of Arizona (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-01-04
- Volume
- 108
- Issue
- 4
- Pages
- 1433-1438
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3029730
- OpenAlex
- W2077950988
- Cited by
- 673
- References
- 47
- Citations by year
- 2026: 41 · 2025: 43 · 2024: 42 · 2023: 48 · 2022: 59 · 2021: 47 · 2020: 65 · 2019: 48 · 2018: 44 · 2017: 52 · 2016: 48 · 2015: 38 · 2014: 36 · 2013: 34 · 2012: 21
- FWCI
- 12.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (ES006694)
- National Institute of Environmental Health Sciences (ES-006694, R01ES015010, P30ES006694)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Keywords
- brusatol, Nrf2, chemoresistance, cisplatin, Keap1, ubiquitination, proteasomal degradation, apoptosis, A549 xenograft, drug detoxification, adjuvant chemotherapy, lung cancer
- MeSH terms
- Animals, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Cisplatin, Drug Synergism, Glutathione, HeLa Cells, Humans, Lung Neoplasms, Mice, Nude, Immunoblotting, Molecular Structure, Signal Transduction, Apoptosis, Xenograft Model Antitumor Assays, Quassins, Intracellular Space, Cell Line, Tumor, Cell Proliferation, NF-E2-Related Factor 2, Mice, Ubiquitination
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