Pharmacologic ascorbate induces neuroblastoma cell death by hydrogen peroxide mediated DNA damage and reduction in cancer cell glycolysis
Open accessAbstract
An ascorbate-mediated production of oxidative stress has been shown to retard tumor growth. Subsequent glycolysis inhibition has been suggested. Here, we further define the mechanisms relevant to this observation. Ascorbate was cytotoxic to human neuroblastoma cells through the production of H2O2, which led to ATP depletion, inhibited GAPDH, and non-apoptotic and non-autophagic cell death. The mechanism of cytotoxicity is different when PARP-dependent DNA repair machinery is active or inhibited. Ascorbate-generated H2O2 damaged DNA, activated PARP, depleted NAD+, and reduced glycolysis flux. NAD+ supplementation prevented ATP depletion and cell death, while treatment with a PARP inhibitor, olaparib, preserved NAD+ and ATP levels but led to increased DNA double-strand breakage and did not prevent ascorbate-induced cell death. These data indicate that in cells with an intact PARP-associated DNA repair system, ascorbate-induced cell death is caused by NAD+ and ATP depletion, while in the absence of PARP activation ascorbate-induced cell death still occurs but is a consequence of ROS-induced DNA damage. In a mouse xenograft model, intraperitoneal ascorbate inhibited neuroblastoma tumor growth and prolonged survival. Collectively, these data suggest that ascorbate could be effective in the treatment of glycolysis-dependent tumors. Also, in cancers that use alternative energy metabolism pathways, combining a PARP inhibitor with ascorbate treatment could be useful.
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Pharmacological ascorbate may damage DNA in tumours in living animals.
“This observation suggests that pharmacological ascorbate can cause DNA damage in in vivo tumours”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [36]
In a xenograft model, daily intraperitoneal high-dose ascorbate (4 g kg−1) slowed neuroblastoma growth and raised tumour CHK2 and H2AX activity.
“daily intraperitoneal injection with high-dose ascorbate (4 g kg−1) inhibited neuroblastoma growth in a xenograft model, and tumours had the increased activity of checkpoint kinase 2 (CHK2) and histone 2AX (H2AX).”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [36]
Cancer cells need large amounts of readily available labile Fe2+ to survive and grow.
“cancer cells have a high demand for easily accessible labile Fe2+ for their survival and growth.”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [36]
That neuroblastoma study did not show an in vivo connection between ascorbate and H2O2 production.
“although an in vivo link between ascorbate and the generation of H2O2 has not been demonstrated in this study36.”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [36]
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The metabolism of tumors in the body
Warburg, O., Wind, F., & Negelein, E. (1927) · Journal of General Physiology · doi:10.1085/jgp.8.6.519 · Cited by 4,416 · see citing works
Sulforhodamine B colorimetric assay for cytotoxicity screening
Vichai, V., & Kirtikara, K. (2006) · Nature Protocols · doi:10.1038/nprot.2006.179 · Cited by 3,679 · see citing works
Recent Advances in Neuroblastoma
Maris, J. M. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0804577 · Cited by 1,991 · see citing works
Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance
Levine, M., Conry-Cantilena, C., Wang, Y., Welch, R. W., Washko, P. W., Dhariwal, K. R., Park, J. B., Lazarev, A., Graumlich, J. F., King, J., et al. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.8.3704 · Cited by 1,325 · see citing works
Intracellular ATP levels determine cell death fate by apoptosis or necrosis.
Eguchi, Y., Shimizu, S., & Tsujimoto, Y. (1997) · PubMed · Cited by 1,249 · see citing works
Chen, Q., Espey, M. G., Krishna, M. C., Mitchell, J. B., Corpe, C. P., Buettner, G. R., Shacter, E., & Levine, M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506390102 · Cited by 1,075 · see citing works
Self-citationVitamin C pharmacokinetics: Implications for oral and intravenous use
Padayatty, S. J., Sun, H., Wang, Y., Riordan, H. D., Hewitt, S. M., Katz, A., Wesley, R. A., & Levine, M. (2004) · Annals of Internal Medicine · doi:10.7326/0003-4819-140-7-200404060-00010 · Cited by 992 · see citing works
Yun, J., Mullarky, E., Lu, C., Bosch, K. N., Kavalier, A., Rivera, K., Roper, J., Chio, I. I. C., Giannopoulou, E. G., Rago, C., et al. (2015) · Science · doi:10.1126/science.aaa5004 · Cited by 913 · see citing works
Chen, Q., Espey, M. G., Sun, A. Y., Pooput, C., Kirk, K. L., Krishna, M. C., Khosh, D. B., Drisko, J., & Levine, M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804226105 · Cited by 854 · see citing works
Self-citationNeuroblastoma: developmental biology, cancer genomics and immunotherapy
Cheung, N. V., & Dyer, M. A. (2013) · Nature reviews. Cancer · doi:10.1038/nrc3526 · Cited by 797 · see citing works
ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS
Alexander, A., Cai, S.-L., Kim, J., Nanez, A., Sahin, M., MacLean, K. H., Inoki, K., Guan, K.-L., Shen, J., Person, M. D., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913860107 · Cited by 717 · see citing works
Chen, Q., Espey, M. G., Sun, A. Y., Lee, J.-H., Krishna, M. C., Shacter, E., Choyke, P. L., Pooput, C., Kirk, K. L., Buettner, G. R., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702854104 · Cited by 676 · see citing works
Self-citationKnight, K. R., Kraemer, D. F., & Neuwelt, E. A. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2004.00.5355 · Cited by 543 · see citing works
Schraufstätter, I. U., Hinshaw, D. B., Hyslop, P. A., Spragg, R. G., & Cochrane, C. G. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112436 · Cited by 511 · see citing works
Ma, Y., Chapman, J., Levine, M., Polireddy, K., Drisko, J., & Chen, Q. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3007154 · Cited by 501 · see citing works
Self-citationAssociation of Age at Diagnosis and Genetic Mutations in Patients With Neuroblastoma
Cheung, N. V. (2012) · JAMA · doi:10.1001/jama.2012.228 · Cited by 467 · see citing works
Schoenfeld, J. D., Sibenaller, Z. A., Mapuskar, K. A., Wagner, B. A., Cramer-Morales, K. L., Furqan, M., Sandhu, S., Carlisle, T. L., Smith, M. C., Abu Hejleh, T., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.02.018 · Cited by 443 · see citing works
Phase I clinical trial of i.v. ascorbic acid in advanced malignancy
Hoffer, L. J., Levine, M., Assouline, S., Melnychuk, D., Padayatty, S. J., Rosadiuk, K., Rousseau, C., Robitaille, L., & Miller, W. H. (2008) · Annals of Oncology · doi:10.1093/annonc/mdn377 · Cited by 375 · see citing works
The contributions of respiration and glycolysis to extracellular acid production
Mookerjee, S. A., Goncalves, R. L. S., Gerencser, A. A., Nicholls, D. G., & Brand, M. D. (2014) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2014.10.005 · Cited by 347 · see citing works
Children's Oncology Group's 2013 blueprint for research: Neuroblastoma
Park, J. R., Bagatell, R., London, W. B., Maris, J. M., Cohn, S. L., Mattay, K. M., & Hogarty, M. D. (2012) · Pediatric Blood & Cancer · doi:10.1002/pbc.24433 · Cited by 334 · see citing works
Apoptosis and necrosis: Intracellular ATP level as a determinant for cell death modes
Tsujimoto, Y. (1997) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400262 · Cited by 322 · see citing works
Mechanisms of Ascorbate-Induced Cytotoxicity in Pancreatic Cancer
Du, J., Martin, S. M., Levine, M., Wagner, B. A., Buettner, G. R., Wang, S.-H., Taghiyev, A. F., Du, C., Knudson, C. M., & Cullen, J. J. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1713 · Cited by 316 · see citing works
Welsh, J. L., Wagner, B. A., Erve, T. J. V. ‘., Zehr, P. S., Berg, D., Halfdanarson, T. R., Yee, N. S., Bodeker, K. L., Du, J., Roberts, L. J., et al. (2013) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-013-2070-8 · Cited by 310 · see citing works
Karpinich, N. O., Tafani, M., Rothman, R. J., Russo, M. A., & Farber, J. L. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110629200 · Cited by 308 · see citing works
Doskey, C. M., Buranasudja, V., Wagner, B. A., Wilkes, J. G., Du, J., Cullen, J. J., & Buettner, G. R. (2016) · Redox Biology · doi:10.1016/j.redox.2016.10.010 · Cited by 301 · see citing works
Ascorbic acid recycling in human neutrophils
Washko, P., Wang, Y., & Levine, M. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)82289-x · Cited by 289 · see citing works
Monti, D., Mitchell, E. P., Bazzan, A. J., Littman, S. J., Zabrecky, G. P., Yeo, C. J., Pillai, M. V., Newberg, A. B., Deshmukh, S., & Levine, M. N. (2012) · PLoS ONE · doi:10.1371/journal.pone.0029794 · Cited by 270 · see citing works
Stephenson, C. M., Levin, R. D., Spector, T., & Lis, C. G. (2013) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-013-2179-9 · Cited by 265 · see citing works
Verrax, J., & Calderón, P. B. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.02.016 · Cited by 232 · see citing works
Vitamin C Antagonizes the Cytotoxic Effects of Antineoplastic Drugs
Heaney, M. L., Gardner, J. R., Karasavvas, N., Golde, D. W., Scheinberg, D. A., Smith, E. A., & O’Connor, O. A. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1490 · Cited by 229 · see citing works
Chen, R., Zou, Y., Mao, D., Sun, D., Gao, G., Shi, J., Liu, X., Zhu, C., Yang, M., Ye, W., et al. (2014) · The Journal of Cell Biology · doi:10.1083/jcb.201403009 · Cited by 191 · see citing works
Pharmacologic ascorbate synergizes with gemcitabine in preclinical models of pancreatic cancer
Espey, M. G., Chen, P., Chalmers, B. P., Drisko, J., Sun, A. Y., Levine, M., & Chen, Q. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.03.007 · Cited by 190 · see citing works
Self-citationAscorbate Reacts with Singlet Oxygen to Produce Hydrogen Peroxide
Kramarenko, G. G., Hummel, S. G., Martin, S. M., & Buettner, G. R. (2006) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.2006.tb09823.x · Cited by 178 · see citing works
Pharmacokinetic model of ascorbic acid in healthy male volunteers during depletion and repletion
Graumlich, J. F., Ludden, T. M., Conry-Cantilena, C., Cantilena, L. R., Wang, Y., & Levine, M. (1997) · Pharmaceutical Research · doi:10.1023/a:1012186203165 · Cited by 172 · see citing works
Ascorbate Reacts with Singlet Oxygen to Produce Hydrogen Peroxide
Kramarenko, G. G., Hummel, S. G., Martin, S. M., et al. (2006) · Photochemistry and Photobiology · doi:10.1562/2006-01-12-rn-774 · Cited by 133 · see citing works
Schoenfeld, J. D., Sibenaller, Z. A., Mapuskar, K. A., Wagner, B. A., Cramer-Morales, K. L., Furqan, M., Sandhu, S., Carlisle, T. L., Smith, M. C., Hejleh, T. A., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.07.008 · Cited by 130 · see citing works
Pharmacological Ascorbate Radiosensitizes Pancreatic Cancer
Du, J., Cieslak, J. A., Welsh, J. L., Sibenaller, Z. A., Allen, B. G., Wagner, B. A., Kalen, A. L., Doskey, C. M., Strother, R. K., Button, A. M., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-1707 · Cited by 112 · see citing works
Washko, P. W., Hartzell, W. O., & Levine, M. (1989) · Analytical Biochemistry · doi:10.1016/0003-2697(89)90243-1 · Cited by 105 · see citing works
Verrax, J., Cadrobbi, J., Marques, C., Taper, H. S., Habraken, Y., Piette, J. G., & Calderón, P. B. (2004) · APOPTOSIS · doi:10.1023/b:appt.0000018804.26026.1a · Cited by 105 · see citing works
Inhibition of PARP prevents oxidant-induced necrosis but not apoptosis in LLC-PK1cells
Filipović, D., Meng, X., & Reeves, W. B. (1999) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.1999.277.3.f428 · Cited by 103 · see citing works
Chen, P., Yu, J., Chalmers, B., Drisko, J., Yang, J., Li, B., & Chen, Q. (2011) · Anti-Cancer Drugs · doi:10.1097/cad.0b013e32834fd01f · Cited by 92 · see citing works
Self-citationNakagawara, A. (1998) · PubMed · Cited by 89 · see citing works
Sodium Ascorbate induces apoptosis in neuroblastoma cell lines by interfering with iron uptake
Carosio, R., Zuccari, G., Orienti, I., Mangraviti, S., & Montaldo, P. G. (2007) · Molecular Cancer · doi:10.1186/1476-4598-6-55 · Cited by 71 · see citing works
Ohtani, S., Iwamaru, A., Deng, W., Ueda, K., Wu, G., Jayachandran, G., Kondo, S., Atkinson, E. N., Minna, J. D., Roth, J. A., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-3884 · Cited by 70 · see citing works
Hong, S.-W., Jin, D.-H., Hahm, E., Yim, S.-H., Lim, J., Kim, K.-I., Yang, Y. D., Lee, S.-S., Kang, J., Lee, W.-J., et al. (2007) · Oncology Reports · doi:10.3892/or.18.4.811 · Cited by 69 · see citing works
Lin, S.-Y., Lai, W.-W., Chou, C., Kuo, H., Li, T., Chung, J., & Yang, J. (2006) · Melanoma Research · doi:10.1097/01.cmr.0000232297.99160.9e · Cited by 63 · see citing works
Moles of a Substance per Cell Is a Highly Informative Dosing Metric in Cell Culture
Doskey, C. M., Erve, T. J. V. ‘., Wagner, B. A., & Buettner, G. R. (2015) · PLoS ONE · doi:10.1371/journal.pone.0132572 · Cited by 62 · see citing works
Kang, J. S., Cho, D., Kim, Y., Hahm, E., Yang, Y., Kim, D., Hur, D., Park, H., Bang, S., Hwang, Y. I., et al. (2003) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-003-0407-6 · Cited by 59 · see citing works
Inhibitors of hydroperoxide metabolism enhance ascorbate-induced cytotoxicity
Olney, K., Du, J., Erve, T. J. V. ‘., Witmer, J. R., Sibenaller, Z. A., Wagner, B. A., Buettner, G. R., & Cullen, J. J. (2012) · Free Radical Research · doi:10.3109/10715762.2012.755263 · Cited by 59 · see citing works
Verrax, J., Dejeans, N., Sid, B., Glorieux, C., & Calderón, P. B. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.07.102 · Cited by 54 · see citing works
The CBS/CSE system: a potential therapeutic target in NAFLD?
Sarna, L. K., Siow, Y. L., & Karmin, O. (2014) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2014-0394 · Cited by 54 · see citing works
Glycolysis–respiration relationships in a neuroblastoma cell line
Swerdlow, R. H., Lezi, E., Aires, D., & Lu, J. (2013) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2013.01.002 · Cited by 47 · see citing works
Self-citationThe unpaved journey of vitamin C in cancer treatment
Chen, Q., Polireddy, K., Chen, P., & Dong, R. (2015) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2014-0509 · Cited by 40 · see citing works
Self-citationManganoporphyrins and ascorbate enhance gemcitabine cytotoxicity in pancreatic cancer
Cieslak, J. A., Strother, R. K., Rawal, M., Du, J., Doskey, C. M., Schroeder, S. R., Button, A. M., Wagner, B. A., Buettner, G. R., & Cullen, J. J. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.02.018 · Cited by 37 · see citing works
Fischer, A. P., & Miles, S. L. (2016) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2016.12.056 · Cited by 31 · see citing works
Synergistic Anticancer Action of Lysosomal Membrane Permeabilization and Glycolysis Inhibition
Kosić, M., Arsikin, K. M., Paunović, V., Firestone, R. A., Ristic, B. Z., Mirčić, A., Petricevic, S. M., Bošnjak, M., Zogovic, N. S., Mandić, M., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.752113 · Cited by 18 · see citing works
Levine, M., & Violet, P.-C. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.03.008 · Cited by 17 · see citing works
Farah, I. O., Lewis, V. L., Ayensu, W. K., & Mahmud, O. (2011) · PubMed · Cited by 6 · see citing works
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1 of the 59 references couldn’t be matched to a known paper.
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Targeting cancer vulnerabilities with high-dose vitamin C
Ngo, B., Van Riper, J. M., Cantley, L. C., & Yun, J. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0135-7 · Cited by 423 · see citing works
Zambonino, M. C., Quizhpe, E. M., Mouheb, L., Rahman, A., Agathos, S. N., & Dahoumane, S. A. (2023) · Nanomaterials · doi:10.3390/nano13030424 · Cited by 193 · see citing works
Yang, J., Ma, S., Xu, R. F., Wei, Y., Zhang, J., Zuo, T., Wang, Z., Deng, H., Yang, N., & Shen, Q. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.04.013 · Cited by 186 · see citing works
Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome
Boretti, A. A., & Banik, B. K. (2020) · PharmaNutrition · doi:10.1016/j.phanu.2020.100190 · Cited by 168 · see citing works
Polireddy, K., Dong, R., Reed, G. A., Yu, J., Chen, P., Williamson, S. K., Violet, P.-C., Pessetto, Z. Y., Godwin, A. K., Fan, F., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-17568-8 · Cited by 153 · see citing works
Self-citationReprogramming the epigenome with vitamin C
Lee Chong, T., Ahearn, E. L., & Cimmino, L. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00128 · Cited by 120 · see citing works
High-Dose Vitamin C for Cancer Therapy
Mussa, A., Idris, R. A. M., Ahmed, N., Ahmad, S., Murtadha, A. H., Din, T. A. D. A. T., Yean, C. Y., Rahman, W. F. W. A., Lazim, N. M., Uskoković, V., et al. (2022) · Pharmaceuticals · doi:10.3390/ph15060711 · Cited by 81 · see citing works
Cold Plasma-Treated Ringer’s Saline: A Weapon to Target Osteosarcoma
Mateu‐Sanz, M., Tornín, J., Brulin, B., Khlyustova, A. V., Ginebra, M., Layrolle, P., & Canal, C. (2020) · Cancers · doi:10.3390/cancers12010227 · Cited by 76 · see citing works
Talib, W. H., Jum'Ah, D., Attallah, Z. S., Jallad, M. S., Kury, L. T. A., Hadi, R. W., & Mahmod, A. I. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1281879 · Cited by 57 · see citing works
Zafar, H., Zhang, J., Raza, F., Pan, X., Hu, Z., Feng, H., & Shen, Q. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.06.059 · Cited by 54 · see citing works
Sestrins as a Therapeutic Bridge between ROS and Autophagy in Cancer
Sánchez-Álvarez, M., Strippoli, R., Donadelli, M., Bazhin, A., & Cordani, M. (2019) · Cancers · doi:10.3390/cancers11101415 · Cited by 49 · see citing works
Hou, J., Qian, M., Zhao, H., Li, Y., Liao, Y., Han, G., Xu, Z., Wang, F., Song, Y., & Liu, Y. (2018) · Analytica Chimica Acta · doi:10.1016/j.aca.2018.03.028 · Cited by 53 · see citing works
Pharmacologic Induction of BRCAness in BRCA-Proficient Cancers: Expanding PARP Inhibitor Use
Abbotts, R., Dellomo, A. J., & Rassool, F. V. (2022) · Cancers · doi:10.3390/cancers14112640 · Cited by 52 · see citing works
High-Dose Vitamin C: Preclinical Evidence for Tailoring Treatment in Cancer Patients
Giansanti, M., Karimi, T., Faraoni, I., & Graziani, G. (2021) · Cancers · doi:10.3390/cancers13061428 · Cited by 50 · see citing works
Lu, B., Wang, Z., Ding, Y., Wang, X., Lu, S., Wang, C., He, C. H., Piao, M., Chi, G., Luo, Y., et al. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.03.046 · Cited by 48 · see citing works
Vaishampayan, P., & Lee, Y. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103288 · Cited by 43 · see citing works
Vitamin C in Cancer: A Metabolomics Perspective
Park, S., Ahn, S., Shin, Y., Yang, Y.-J., & Yeom, C. H. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00762 · Cited by 44 · see citing works
Buranasudja, V., Doskey, C. M., Gibson, A. R., Wagner, B. A., Du, J., Gordon, D. J., Koppenhafer, S. L., Cullen, J. J., & Buettner, G. R. (2019) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-19-0381 · Cited by 37 · see citing works
Dachs, G. U., Gandhi, J., Wohlrab, C., Carr, A. C., Morrin, H. R., Pullar, J. M., Bayer, S. B., Eglinton, T., Robinson, B. A., & Vissers, M. C. M. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2020.600715 · Cited by 30 · see citing works
Vitamin C, From Supplement to Treatment: A Re-Emerging Adjunct for Cancer Immunotherapy?
Kouakanou, L., Peters, C., Brown, C. E., Kabelitz, D., & Wang, L. D. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.765906 · Cited by 30 · see citing works
Bakalova, R., Zhelev, Z., Miller, T. J., Aoki, I., & Higashi, T. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101357 · Cited by 26 · see citing works
Lee, H., Chen, Y., Chang, W., Li, W., Ke, H., Wu, W., & Kuo, P. (2019) · Medicina · doi:10.3390/medicina55120768 · Cited by 25 · see citing works
Crake, R., Burgess, E. R., Royds, J. A., Phillips, E., Vissers, M. C. M., & Dachs, G. U. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.619300 · Cited by 24 · see citing works
Lee, Y., Chang, W., Chang, C.-P., Liu, T., Chuang, C., Qian, K., Zheng, Y. G., & Li, C. (2019) · Scientific Reports · doi:10.1038/s41598-018-38394-6 · Cited by 24 · see citing works
Ma, Y., Chen, P., Drisko, J., Khabele, D., Godwin, A. K., & Chen, Q. (2020) · Oncology Letters · doi:10.3892/ol.2020.11364 · Cited by 22 · see citing works
Self-citationInsight into the roles of vitamins C and D against cancer: Myth or truth?
Zhao, C., Li, Y., Meng, X., Li, S., Liu, Q., Tang, G., Gan, R., & Li, H. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.05.039 · Cited by 22 · see citing works
GAPDH in neuroblastoma: Functions in metabolism and survival
Cornett, K., Puderbaugh, A., Back, O., & Craven, R. J. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.979683 · Cited by 22 · see citing works
David, E., Viswanathan, T., Prabu, S., & Palanisami, N. (2019) · New Journal of Chemistry · doi:10.1039/c9nj01471c · Cited by 22 · see citing works
Balanced Duality: H2O2-Based Therapy in Cancer and Its Protective Effects on Non-Malignant Tissues
Zaher, A., Petronek, M. S., Allen, B. G., & Mapuskar, K. A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25168885 · Cited by 23 · see citing works
Zhang, L., Qian, M., Xia, J., Chen, L., Cui, H., Xia, Y., Xu, L., Wang, J., & Peng, X. (2018) · Journal of Photochemistry and Photobiology A Chemistry · doi:10.1016/j.jphotochem.2018.10.030 · Cited by 21 · see citing works
Enhanced Anticancer Efficacy of Alkaline Plasma-Activated Water through Augmented RONS Production
Pang, B., Liu, Z., Gao, Y., Li, X., Wang, S., Qi, M., Zhao, X., Fan, R., Xu, D., Cullen, P. J., et al. (2024) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.4c16518 · Cited by 20 · see citing works
Oronowicz, J., Reinhard, J., Reinach, P. S., Ludwiczak, S., Luo, H., Salem, M. H. O. B., Kraemer, M. M., Biebermann, H., Kakkassery, V., & Mergler, S. (2020) · Laboratory Investigation · doi:10.1038/s41374-020-00485-2 · Cited by 20 · see citing works
Antioxidant and antigenotoxic properties of Alpinia galanga, Curcuma amada, and Curcuma caesia
Nag, A., Banerjee, R., Goswami, P., Bandyopadhyay, M., & Mukherjee, A. (2021) · Asian Pacific Journal of Tropical Biomedicine · doi:10.4103/2221-1691.319571 · Cited by 20 · see citing works
Vitamin C (Ascorbate) and Redox Topics in Cancer
Glorieux, C., & Calderón, P. B. (2021) · Antioxidants and Redox Signaling · doi:10.1089/ars.2020.8233 · Cited by 20 · see citing works
Wang, S., Yang, X., Hou, X., & Zhu, Z. (2022) · Process Biochemistry · doi:10.1016/j.procbio.2022.10.022 · Cited by 19 · see citing works
Nagaya, M., Hara, H., Kamiya, T., & Adachi, T. (2019) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2019.108155 · Cited by 19 · see citing works
Role of Vitamin C in Targeting Cancer Stem Cells and Cellular Plasticity
Lee, Y. (2023) · Cancers · doi:10.3390/cancers15235657 · Cited by 18 · see citing works
Neuroactivity of naturally occurring proaporphine alkaloid, pronuciferine
Bayazeid, O., Nemutlu, E., Eylem, C. C., & Yalçın, F. N. (2020) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.22601 · Cited by 15 · see citing works
Levine, M. N., Ebenuwa, I., & Violet, P.-C. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-805378-2.00018-8 · Cited by 15 · see citing works
Sanookpan, K., Chantaravisoot, N., Kalpongnukul, N., Chuenjit, C., Wattanathamsan, O., Shoaib, S., Pithi Chanvorachote, B., & Buranasudja, V. (2023) · Antioxidants · doi:10.3390/antiox12091775 · Cited by 14 · see citing works
Ye, M., Pang, N., Wan, T., Huang, Y., Wei, T., Jiang, X., Zhou, Y., Huang, Y., Yang, H., Zhang, Z., et al. (2019) · Journal of Cancer · doi:10.7150/jca.28087 · Cited by 14 · see citing works
Wu, Z., Chen, B., Gan, Z., Chen, F., & Luo, X. (2020) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.9b01183 · Cited by 14 · see citing works
Cao, X., Yi, Y., Ji, M., Liu, Y., Wang, D., & Zhu, H. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2025.1633447 · Cited by 13 · see citing works
Xiong, Y., Xu, S. S., Fu, B., Tang, W., Zaky, M. Y., Tian, R., Yao, R., Zhang, S., Zhao, Q., Nian, W., et al. (2022) · Food and Chemical Toxicology · doi:10.1016/j.fct.2022.113321 · Cited by 13 · see citing works
Demiray, M. (2020) · Integrative Cancer Therapies · doi:10.1177/1534735420969812 · Cited by 13 · see citing works
Liu, Y., Zhang, L., Ma, Z., Li, T., Liu, Y., Liu, Y., Chen, Q., Li, Y., & Ma, E. (2019) · Free Radical Research · doi:10.1080/10715762.2019.1628957 · Cited by 12 · see citing works
Self-citationIron oxide nanozymes enhanced by ascorbic acid for macrophage-based cancer therapy
Yi, Z., Yang, X., Liang, Y., & Tong, S. (2024) · Nanoscale · doi:10.1039/d4nr01208a · Cited by 11 · see citing works
The discovery of an anti-Candida xanthone with selective inhibition of Candida albicans GAPDH
Chen, X., Zhou, T., Zhou, Z.-D., Fang, Z.-H., Wang, K., Zhang, C., Kong, L., & Yang, M. (2024) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2024.107172 · Cited by 10 · see citing works
In Vitro Cell Density Determines the Sensitivity of Hepatocarcinoma Cells to Ascorbate
Fan, H., Liu, S.-T., Chang, Y., Chiu, Y., Huang, S., & Chen, T.-W. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.843742 · Cited by 9 · see citing works
Huang, Y., Guo, J. Z., & Zhang, J. (2020) · Applied Sciences · doi:10.3390/app10134510 · Cited by 9 · see citing works
Heme-mediated selection of encapsulated Streptococcus pneumoniae in the lungs by oxidative stress
Alibayov, B., Vidal, A. G. J., Murin, L., Scasny, A., Takeshita, K., Beeton, K., Edwards, K. S., Punshon, T., Jackson, B. P., McDaniel, L. S., et al. (2025) · Emerging Microbes & Infections · doi:10.1080/22221751.2025.2532685 · Cited by 8 · see citing works
Zaher, A., Mapuskar, K. A., Sarkaria, J. N., Spitz, D. R., Petronek, M. S., & Allen, B. G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242417158 · Cited by 8 · see citing works
Testa, U., Pelosi, E., & Castelli, G. (2020) · Hematology/Oncology and Stem Cell Therapy · doi:10.1016/j.hemonc.2020.11.002 · Cited by 8 · see citing works
Metabolic interaction of hydrogen peroxide and hypoxia in zebrafish fibroblasts
Dikova, V., Vorhauser, J., Geng, A., Pelster, B., & Sandbichler, A. M. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.11.015 · Cited by 7 · see citing works
Oxidative Stress and DNA Epigenetic Modifications in Cancer: Mechanisms and Targeted Therapeutics
Yang, X., Chen, Q., Yu, Y., Zang, Y., Zheng, R., Zhang, Z., Lu, S., & Zhou, L. (2026) · MedComm – Oncology · doi:10.1002/mog2.70065 · Cited by 6 · see citing works
Self-citationLv, Z., Ali, A., Zou, C., Wang, Z., Ma, M., Cheng, N., Shad, M., Hao, H., Zhang, Y., & Rahman, F. (2024) · Dalton Transactions · doi:10.1039/d4dt01243g · Cited by 5 · see citing works
Saitoh, Y., Takeda, K., Okawachi, K., & Tanimura, Y. (2024) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2024.130738 · Cited by 5 · see citing works
Singhania, M., Sho, S., Fath, M. A., Sanchez, A., Pulliam, C. F., Allen, B. G., Buettner, G. R., Goswami, P. C., Spies, M., Petronek, M. S., et al. (2025) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2025.09.013 · Cited by 5 · see citing works
Vitamin C biochemistry: From scurvy to COVID-19 treatment
Zakić, T., Soskic, M. B., Kalezic, A., Korać, A., Janković, A., & Korać, B. (2020) · Hrana i ishrana · doi:10.5937/hraish2002059z · Cited by 4 · see citing works
Ge, P., Tao, X., Qu, J., He, J., Xing, C., Wang, S., Zhao, Y., Yu, S., Xu, J., Wang, L., et al. (2026) · International Journal of Nanomedicine · doi:10.2147/ijn.s559426 · Cited by 3 · see citing works
Saitoh, Y. (2018) · Free Radical Research · doi:10.1080/10715762.2018.1524891 · Cited by 3 · see citing works
Wu, Z., Yang, B., Qu, W., Lu, J., Li, Y., Wang, J., Yao, R., Li, Y., Geng, Z., & Wang, Z. (2025) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2025.137836 · Cited by 3 · see citing works
Gordon, N., Gallagher, P. T., Richter, O. I., Neupane, N. P., Mandigo, A. C., McCann, J. J., Dylgjeri, E., Vasilevskaya, I. A., McNair, C. M., Paller, C. J., et al. (2026) · Molecular Oncology · doi:10.1002/1878-0261.70183 · Cited by 3 · see citing works
Adachi, T. (2022) · Thermal Medicine · doi:10.3191/thermalmed.38.1 · Cited by 3 · see citing works
Ma, Y., Wu, Y., Wang, X., Gao, G., & Zhou, X. M. (2023) · Chinese Journal of Organic Chemistry · doi:10.6023/cjoc202206044 · Cited by 1 · see citing works
Li, L., Lu, F., Shu, S., Jiang, X., Lu, H., Cao, K., Chen, Z., Gao, J., Liu, M., Chang, L., et al. (2025) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.70993 · Cited by 1 · see citing works
Yazdanparast, S. M., Manoochehri, N., & Abdolahad, M. (2026) · Biomedicines · doi:10.3390/biomedicines14040936 · Cited by 1 · see citing works
Singh, F. (2026) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.70851 · Cited by 1 · see citing works
Peskin, A. V. (2026) · Cells · doi:10.3390/cells15131212 · Cited by 1 · see citing works
Possible new mitochondrial mechanism of vitamin C anticancer activity
Lemeshko, V. V. (2022) · Revista de la Academia Colombiana de Ciencias Exactas Físicas y Naturales · doi:10.18257/raccefyn.1575 · Cited by 1 · see citing works
Dachs, G. U., Gandhi, J., Wohlrab, C., Carr, A. C., Morrin, H. R., Pullar, J. M., Bayer, S. B., Eglinton, T., Robinson, B. A., & Vissers, M. C. M. (2020) · doi:10.21203/rs.3.rs-65137/v1 · Cited by 1 · see citing works
Zhou, L., Zhao, X., Wang, S., Lv, H., Shaikh, A. B., & Shang, P. (2020) · Research Square · doi:10.21203/rs.3.rs-69358/v1
Hussien, H., Elbolok, A. H., Elgayar, S. F., & Sholqamy, M. A. (2021) · Journal of Modern Research · doi:10.21608/jmr.2021.102961.1084
Ou, J., Liao, Q., Du, Y., Xi, W., Meng, Q., Li, K., Cai, Q., & Pang, C. L. K. (2022) · Research Square · doi:10.21203/rs.3.rs-1472206/v1
Vitamin C: is there a place in anticancer treatment?
Gerk, I., & Moiseenko, V. M. (2022) · Practical oncology · doi:10.31917/2303133
Ascorbate induces G2/M arrest and necrosis without generation of direct DNA double-strand breaks
Hariri, M., Papalanis, E., Spiegelberg, D., Plotnikov, E. V., Viktorsson, K., & Stenerlöw, B. (2025) · Heliyon · doi:10.1016/j.heliyon.2025.e43964
Ascorbate-driven quinone redox cycling as a pro-oxidant anticancer strategy
Glorieux, C., Enriquez-Lara, C., Valderrama, J. A., Benites, J. F., & Calderón, P. B. (2026) · Redox Biology · doi:10.1016/j.redox.2026.104274 · Cited by 1 · see citing works
Sensitizing Colorectal Cancer to PARP Inhibitors: Biomarkers, Mechanisms, and Combination Strategies
Elesnawy, M., Masood, E., & Naik, A. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27188127
- Authors
- Ma, E., Chen, P., Wilkins, H. M., Wang, T., Swerdlow, R. H., & Chen, Q.
- Affiliations
- Shenyang Pharmaceutical University (CN)
- University of Kansas Medical Center (US)
- Corresponding author
- Chen, Qi
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2017-12
- Volume
- 113
- Pages
- 36-47
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC5856454
- OpenAlex
- W2755332177
- Cited by
- 79
- References
- 59
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 9 · 2023: 5 · 2022: 10 · 2021: 8 · 2020: 13 · 2019: 12 · 2018: 6 · 2017: 2
- FWCI
- 7.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Free Radical Biology and Medicine (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Kansas
- P30 (AG035982)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Keywords
- vitamin C, neuroblastoma, hydrogen peroxide, oxidative stress, DNA damage, poly(ADP-ribose) polymerase, NAD+ depletion, ATP depletion, glycolysis inhibition, glyceraldehyde-3-phosphate dehydrogenase, non-apoptotic cell death, olaparib, PARP inhibitors, DNA double-strand breaks, tumor growth inhibition, cancer metabolism
- MeSH terms
- Animals, Ascorbic Acid, DNA, DNA Damage, DNA Repair, Humans, Hydrogen Peroxide, Neuroblastoma, Poly(ADP-ribose) Polymerases, Cell Death, Oxidative Stress, Xenograft Model Antitumor Assays, Mice
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