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Antioxidants May Protect Cancer Cells from Apoptosis Signals and Enhance Cell Viability

  • Akan, Zafer (Department of Biophysics, School of Medicine, Yuzuncu Yil University) ;
  • Garip, Ayse Inhan (Department of Biophysics, School of Medicine, Marmara University)
  • Published : 2013.08.30

Abstract

Quercetin is one of the most abundant dietary flavonoids widely present in many fruits and vegetables. Previous in vitro studies has shown that quercetin acts as an antioxidant and anti-inflammatory agent and it has potent anticarcinogenic properties as an apoptosis inducer. In this study we examined apoptotic effects of quercetin on the K562 erythroleukemia cell line. K562 cells were induced to undergo apoptosis by hydrogen peroxide. Cell viability and apoptosis level were assessed by annexin V and PI staining methods using flow cytometry. Viability of K562 cells was increased by low dose of quercetin (5-100 ${\mu}M$) for 3 hours. High doses of quercetin proved toxic (100-500 ${\mu}M$, 24 hours) and resulted in decrease of K562 cell viability as expected (p<0.01). As to results, 100 ${\mu}M$ quercetin was defined as a protective dose. Also, K562 cell apoptosis due to hydrogen peroxide was decreased in a dose dependent manner. As indicated in previous studies, reduction of superoxides by free radical scavengers like quercetin could be beneficial for prevention of cancer but consumption of such flavonoids during cancer treatment may weaken effects of chemotherapeutics and radiotherapy. Especially cancer patients should be carefully considered for traditional phytotherapy during cancer treatment, which can lead to controversial results.

Keywords

References

  1. Bayir H (2005). Reactive oxygen species. Crit Care Med, 33, 498-501. https://doi.org/10.1097/01.CCM.0000186787.64500.12
  2. Benkovic V, Knezevic AH, Dikic D, et al (2009). Radioprotective effects of quercetin and ethanolic extract of propolis in gamma-irradiated mice. Arh Hig Rada Toksikol, 60, 129-38.
  3. Cao XG, Li XX, Bao YZ, et al (2007). Responses of human lens epithelial cells to quercetin and DMSO. Invest Ophthalmol Vis Sci, 48, 3714-8. https://doi.org/10.1167/iovs.06-1304
  4. Chamond RR, Anon JC, Guerra P, et al (1999). Apoptosis and disease. Alergol Immunol Clin, 14, 367-74.
  5. Chow JM, Shen SC, Huan SK (2005). Quercetin, but not rutin and quercitrin, prevention of $H_{2}O_{2}$-induced apoptosis via anti-oxidant activity and heme oxygenase 1 gene expression in macrophages. Biochem Pharmacol, 69, 1839-51. https://doi.org/10.1016/j.bcp.2005.03.017
  6. Davis JM, Murphy EA, Carmichael MD (2009). Effects of the dietary flavonoid quercetin upon performance and health. Curr Sports Med Rep, 8, 206-13. https://doi.org/10.1249/JSR.0b013e3181ae8959
  7. Formica JV, Regelson W (1995). Review of the biology of Quercetin and related bioflavonoids. Food Chem Toxicol, 33, 1061-80. https://doi.org/10.1016/0278-6915(95)00077-1
  8. Gerhauser C (2008). Cancer chemopreventive potential of apples, apple juice, and apple components. Planta Med, 74, 1608-24. https://doi.org/10.1055/s-0028-1088300
  9. Hertog MG, Hollman PC (1996). Potential health effects of the dietary flavonol quercetin. Eur J Clin Nutr, 50, 63-71.
  10. Hultqvist M, Olsson LM, Gelderman KA, et al (2009). The protective role of ROS in autoimmune disease. Trends Immunol, 30, 201-8. https://doi.org/10.1016/j.it.2009.03.004
  11. Ishikawa Y, Kitamura M (2000). Anti-apoptotic effect of quercetin; intervention in the JNK- and ERK-mediated apoptotic pathways. Kidney Int, 58, 1078-87. https://doi.org/10.1046/j.1523-1755.2000.00265.x
  12. Jung JH, Lee JO, Kim JH, et al (2010). Quercetin suppresses HeLa cell viability via AMPK-induced HSP70 and EGFR down-regulation. J Cell Physiol, 223, 408-14.
  13. Kopani M, Celec P, Danisovic L, et al (2006). Oxidative stress and electron spin resonance. Clin Chim Acta, 364, 61-6. https://doi.org/10.1016/j.cca.2005.05.016
  14. Kulbacka J, Saczko J, Chwilkowska A (2009). Oxidative stress in cells damage processes. Pol Merkur Lekarski, 27, 44-7.
  15. Murakami A, Ashida H, Terao J (2008). Multitargeted cancer prevention by quercetin. Cancer Lett, 269, 315-25. https://doi.org/10.1016/j.canlet.2008.03.046
  16. Nguyen TT, Tran E, Nguyen TH, et al (2004). The role of activated MEK-ERK pathway in quercetin-induced growth inhibition and apoptosis in A549 lung cancer cells. Carcinogenesis, 25, 647-59.
  17. Orsolic N, Benkovic V, Horvat-Knezevic A, et al (2007). Assessment by survival analysis of the radioprotective properties of propolis and its polyphenolic compounds. Biol Pharm Bull, 30, 946-51. https://doi.org/10.1248/bpb.30.946
  18. Park C, So HS, Shin CH, et al (2003). Quercetin protects the hydrogen peroxide-induced apoptosis via inhibition of mitochondrial dysfunction in H9c2 cardiomyoblast cells. Biochem Pharmacol, 66, 1287-95. https://doi.org/10.1016/S0006-2952(03)00478-7
  19. Rinaldi S, Landucci F, De Gaudio AR (2009). Antioxidant therapy in critically septic patients. Curr Drug Targets, 10, 872-80. https://doi.org/10.2174/138945009789108774
  20. Richter M, Ebermann R, Marian B (1999). Quercetin-induced apoptosis in colorectal tumor cells; possible role of EGF receptor signaling. Nutr Cancer, 34, 88-99. https://doi.org/10.1207/S15327914NC340113
  21. Schafer FQ, Buettner GR (2001). Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med, 30, 1191-212. https://doi.org/10.1016/S0891-5849(01)00480-4
  22. Siu D (2010). A new way of targeting to treat coronary artery disease. J Cardiovasc Med (Hagerstown), 11, 1-6. https://doi.org/10.2459/JCM.0b013e32832e0af3
  23. Terao J (2009). Dietary flavonoids as antioxidants. Forum Nutr, 61, 87-94. https://doi.org/10.1159/000212741
  24. Ueno I, Kohno M, Haraikawa K, et al (1984). Interaction between quercetin and superoxide radicals. Reduction of the quercetin mutagenicity. J Pharmacobiodyn, 7, 798-803. https://doi.org/10.1248/bpb1978.7.798
  25. Van Erk MJ, Roepman P, van der Lende TR, et al (2005). Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr, 44, 143-56. https://doi.org/10.1007/s00394-004-0503-1

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