Abstract
Plant-derived dietary antioxidants have attracted considerable interest in recent past for their ability to induce apoptosis and regression of tumors in animal models. While it is believed that the antioxidant properties of these agents may contribute to lowering the risk of cancer induction by impeding oxidative injury to DNA, it could not account for apoptosis induction and chemotherapeutic observations. We have provided a number of evidence that dietary antioxidants can alternatively switch to a pro-oxidant action in the presence of transition metals such as copper. Such a pro-oxidant action leads to strand breaks in cellular DNA and growth inhibition in cancer cells.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Asensi M, Medina I, Ortega A, Corretera J, Carmen-Bano M, Obrador E, Estrela MJ (2002) Inhibition of cancer growth by resveratrol is related to its low bioavailability. Free Radic Biol Med 33:387–398
Azmi AS, Bhat SH, Hanif S, Hadi SM (2006) Plant polyphenols mobilize endogenous copper in human peripheral lymphocytes leading to oxidative DNA breakage: a putative mechanism for anticancer properties. FEBS Lett 580:533–538
Bjeldanes LF, Chang GW (1977) Mutagenic activity of quercetin and related compounds. Science 197:577–578
Chen Q, Espey MG, Sun AY, Pooput C, Kirk KL, Krishna MC, Khosh DB, Drisko J, Levine M (2008) Pharmacologic doses of ascorbate act as a prooxidant and decrease growth aggressive tumor xenografts in mice. Proc Natl Acad Sci U S A 105:11105–11109
Clement MV, Long LH, Ramalingam J, Halliwell B (2002) The cytotoxicity of dopamine may be an artifact of cell culture. J Neurochem 81:414–421
Elizabeth GP, Navdeep SC, David AT (2014) The promise and perils of antioxidants for cancer patients. N Engl J Med 371:177
Garg AK, Buchholz TA, Aggarwal BB (2005) Chemosensitization and radiosensitization of tumors by plant polyphenols. Antioxid Redox Signal 7:1630–1647
Govindaraju M, Shekar HS, Sateesha SB, Vasudeva P, Raju KR, Rao S, Rao KSJ, Rajamma AJ (2013) Copper interactions with DNA of chromatin and its role in neurodegenerative disorders. J Pharm Anal 3:354–359
Gupte A, Mumper RG (2008) Elevated copper and oxidative stress in cancer cells as a target for cancer treatment. Cancer Treat Rev 35:32–46
Hadi SM, Asad SF, Singh S, Ahmad A (2000) Putative mechanism for anticancer and apoptosis inducing properties of plant derived polyphenolic compounds. IUBMB Life 50:167–171
Hadi SM, Bhat SH, Azmi AS, Hanif S, Shamim U, Ullah MF (2007) Oxidative breakage of cellular DNA by plant polyphenols: a putative mechanism for anticancer properties. Semin Cancer Biol 17:370–376
Hadi SM, Ullah MF, Azmi AS, Ahmad A, Shamim U, Zubair H, Khan HY (2010) Resveratrol mobilizes endogenous copper in human peripheral lymphocytes leading to oxidative DNA breakage: a putative mechanism for chemoprevention of cancer. Pharm Res 27:979–988
Halliwell B (2003) Oxidative stress in cell culture: an under appreciated problem? FEBS Lett 540:3–6
Inoue M, Suzuki R, Koide T, Sakaguchi N, Ogihara Y, Yabu Y (1994) Antioxidant, gallic acid, induces apoptosis in HL60RG cells. Biochem Biophys Res Commun 204:898–904
Jain A, Martin MC, Parveen N, Khan NU, Parish JH, Hadi SM (1999) Reactivities of flavonoids with different hydroxyl substituents for the cleavage of DNA in the presence of Cu(II). Phytother Res 13:1–4
Khan HY, Zubair H, Faisal M, Ullah MF, Farhan M, Sarkar FH, Ahmad A, Hadi SM (2014) Plant polyphenol induced cell death in human cancer cells involves mobilization of intracellular copper ions and reactive oxygen species generation: a mechanism for cancer chemopreventive action. Mol Nutr Food Res 58:437–446
Lavie O, Barnett-Griness O, Narod SA, Rennert G (2008) The risk of developing uterine sarcoma after tamoxifen use. Int J Gynecol Cancer 18:352–356
Rahman A, Shahabuddin A, Hadi SM, Parish JH, Ainley K (1989) Strand scission in DNA induced by quercetin and Cu(II): role of Cu(I) and oxygen free radicals. Carcinogenesis 10:1833–1839
Sayin VI, Ibrahim MX, Larsson E, Nilsson JA, Lindahl P, Bergo MO (2014) Antioxidants accelerate lung cancer progression in mice. Sci Transl Med 6:221ra15
Shamim U, Hanif S, Ullah MF, Azmi AS, Hadi SM (2008) Plant polyphenols mobilize nuclear copper in human peripheral lymphocytes leading to oxidatively generated DNA breakage: implications for an anticancer mechanism. Free Radic Res 42:764–772
Ullah MF, Khan HY, Zubair H, Shamim U, Hadi SM (2011) The antioxidant ascorbic acid mobilizes nuclear copper leading to a prooxidant breakage of cellular DNA: implications for chemotherapeutic action against cancer. Cancer Chemother Pharmacol 67:103–110
Vainio H, Weiderpress E (2006) Fruit and vegetables in cancer prevention. Nutr Cancer 54:111–142
Vollbracht C, Schneider B, Leendert V, Weiss G, Auerbach L, Beuth J (2011) Intravenous vitamin C administration improves quality of life in breast cancer patients during chemo-/radiotherapy and aftercare: results of a retrospective, multicentre, epidemiological cohort study in Germany. In Vivo 25:983–990
Watson J (2013) Oxidants, antioxidants and the current incurability of metastatic cancers. Open Biol 3:120144
Yen GC, Duh PD, Tsai HL (2002) Antioxidant and pro-oxidant properties of ascorbic acid and gallic acid. Food Chem 79:307–313
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Hadi, S., Farhan, M. (2016). Making Sense of Antioxidant–Pro-oxidant Conundrum in Anticancer Research. In: Ullah, M., Ahmad, A. (eds) Critical Dietary Factors in Cancer Chemoprevention. Springer, Cham. https://doi.org/10.1007/978-3-319-21461-0_3
Download citation
DOI: https://doi.org/10.1007/978-3-319-21461-0_3
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-21460-3
Online ISBN: 978-3-319-21461-0
eBook Packages: Chemistry and Materials ScienceChemistry and Material Science (R0)