Effect of selected catechins on doxorubicin antiproliferative efficacy and hepatotoxicity in vitro

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Abstract

Catechins may influence both desirable and undesirable effects of many drugs. In this study, the in vitro effect of (+)-catechin, (-)-epicatechin, (-)-epigallocatechin, (-)-epicatechin gallate, and (-)-epigallocatechin gallate (EGCG) on the efficacy of anticancer drug doxorubicin (DOX) was studied in HCT-8 cancer cells. Rat hepatocytes were used to study the influence of EGCG on DOX hepatotoxicity. Cell proliferation and viability were studied by 3-[4,5-dimethylthiazol- 2-yl]-2,5-diphenyl tetrazolium bromide and neutral red uptake test assays. Formation of reactive oxygen species (ROS) was determined using the dichlorofluorescein assay. All of the studied catechins (1-25 μmol L-1) had no effect on the proliferation of intestinal cancer cells and did not affect the antiproliferative effect of DOX (1-8 μmol L-1) in these cells. Moreover, EGCG at 25 μmol L-1 increased the viability of isolated hepatocytes and significantly protected these cells against DOX-induced toxicity and ROS production. Consumption of EGCG during DOX therapy seems to be safe and beneficial, since EGCG does not decrease DOX anticancer efficacy and could ameliorate DOX hepatotoxicity

1. R. Ng, N. Better and M. Green, Anticancer agents and cardiotoxicity, Semin. Oncol. 33 (2006) 2-14; DOI: 10.1053/j.seminoncol.2005.11.001.

2. K. Schimmel, D. Richel, R. van den Brink and H. J. Guchelaar, Cardiotoxicity of cytotoxic drugs, Cancer Treat. Rev. 30 (2004) 181-191; DOI: 10.1016/j.ctrv.2003.07.003.

3. T. Simunek, M. Sterba, O. Popelova, M. Adamcová, R. Hrdina and V. Gersl, Anthracycline-induced cardiotoxicity: overview of studies examining the roles of oxidative stress and free cellular iron, Pharmacol. Rep. 61 (2009) 154-171.

4. S. Kalender, Y. Kalender, A. Ates, M. Yel, E. Olcay and S. Candan, Protective role of antioxidant vitamin E and catechin on idarubicin-induced cardiotoxicity in rats, Braz. J. Med. Biol. Res. 35 (2002) 1379-1387; DOI: 10.1590/s0100-879x2002001100017.

5. Y. Kalender, M. Yel and S. Kalender, Doxorubicin hepatotoxicity and hepatic free radical metabolism in rats - the effects of vitamin E and catechin, Toxicology 209 (2005) 39-45; DOI: 10.1016/j.tox.2004.12.003.

6. J. H. Doroshow, Prevention of doxorubicin-induced killing of MCF-7 human breast cancer cells by oxygen radical scavengers and iron chelating agents, Biochem. Biophys. Res. Commun. 135 (1986) 330-335; DOI: 10.1016/0006-291x(86)90981-2.

7. B. K. Sinha, A. G. Katki, G. Batist, K. H. Cowan and C. E. Myers, Adriamycin-stimulated hydroxyl radical formation in human breast tumor cells, Biochem. Pharmacol. 36 (1987) 793-796; DOI: 10.1016/0006-2952(87)90164-x.

8. A. L. A. Ferreira, L. S. Matsubara andB. B. Matsubara, Anthracycline-induced cardiotoxicity, Cardiovasc. Hematol. Agents Med. Chem. 6 (2008) 278-281; DOI: 10.2174/187152508785909474.

9. C. Carvalho, R. X. Santos, S. Cardoso, S. Correia, P. J. Oliveira, M. S. Santos and P. I. Moreira, Doxorubicin: the good, the bad and the ugly effect, Curr. Med. Chem. 16 (2009) 3267-3285; DOI: 10.2174/092986709788803312.

10. Y. Chen, P. Jungsuwadee, M. Vore, D. A. Butterfield and D. K. St Clair, Collateral damage in cancer chemotherapy: oxidative stress in nontargeted tissues, Mol. Interv. 7 (2007) 147-156; DOI: 10.1124/mi.7.3.6.

11. A. Mohan, S. Narayanan, S. Sethuraman and U. M. Krishnan, Combinations of plant polyphenols & anti-cancer molecules: a novel treatment strategy for cancer chemotherapy, Anti-Cancer Agents Med. Chem. 13 (2013) 281-295; DOI: 10.2174/1871520611313020015.

12. V. Hanušová, I. Boušová and L. Skálová, Possibilities to increase the effectiveness of doxorubicin in cancer cells killing, Drug Metab. Rev. 43 (2011) 540-557; DOI: 10.3109/03602532.2011. 609174.

13. H. K. Biesalski and J. Frank, Antioxidants in cancer therapy: is there a rationale to recommend antioxidants during cancer therapy? Biofactors 17 (2003) 229-240; DOI: 10.1002/biof.5520170122.

14. K. A. Conklin, Cancer chemotherapy and antioxidants, J. Nutr. 134 (2004) 3201S-3204S.

15. D. Procházková, I. Boušová and N. Wilhelmová, Antioxidant and prooxidant properties of flavonoids, Fitoterapia 82 (2011) 513-523; DOI: 10.1016/j.fitote.2011.01.018.

16. L. Patil and R. Balaraman, Effect of green tea extract on doxorubicin induced cardiovascular abnormalities: antioxidant action, Iran. J. Pharm. Res. 10 (2011) 89-96.

17. Y. Du and H. X. Lou, Catechin and proanthocyanidin B4 from grape seeds prevent doxorubicin- -induced toxicity in cardiomyocytes, Eur. J. Pharmacol. 591 (2008) 96-101; DOI: 10.1016/j.ejphar. 2008.06.068.

18. J. Zheng, H. C. M. Lee, M. M. bin Sattar, Y. Huang and J. S. Bian, Cardioprotective effects of epigallocatechin-3-gallate against doxorubicin-induced cardiomyocyte injury, Eur. J. Pharmacol. 652 (2011) 82-88; DOI: 10.1016/j.ejphar.2010.10.082.

19. R. H. Mohamed, R. A. Karam and M. G. Amer, Epicatechin attenuates doxorubicin-induced brain toxicity: critical role of TNF-alpha, iNOS and NF-kappa B, Brain Res. Bull. 86 (2011) 22-28; DOI: 10.1016/j.brainresbull.2011.07.001.

20. K. Sato, K. Sueoka, R. Tanigaki, H. Tajima, A. Nakabayashi, Y. Yoshimura and Y. Hosoim, Green tea extracts attenuate doxorubicin-induced spermatogenic disorders in conjunction with higher telomerase activity in mice, J. Assist. Reprod. Genet. 27 (2010) 501-508; DOI: 10.1007/s10815-010- -9438-z.

21. N. Kassner, K. Huse, H. J. Martin, U. Gödtel-Armbrust, A. Metzger, I. Meineke, J. Brockmöller, K. Klein, U. M. Zanger, E. Maser and L. Wojnowski, Carbonyl reductase 1 is a predominant doxorubicin reductase in the human liver, Drug Metab. Dispos. 36 (2008) 2113-2120; DOI: 10.1124/dmd.108.022251.

22. W. X. Huang, L. Y. Ding, Q. A. Huang, H. Hu, S. Liu, X. Yang, X. Hu, Y. Dang, S. Shen, J. Li, X. Ji, S. Jiang, J. O. Liu and L. Yu, Carbonyl reductase 1 as a novel target of (-)-epigallocatechin gallate against hepatocellular carcinoma, Hepatology 52 (2010) 703-714; DOI: 10.1002/hep.23723.

23. M. N. Berry, A. Edwards and G. Barritt, Isolated Hepatocytes: Preparation, Properties and Applications, Elsevier Science Publishers, Amsterdam 1991, pp. 15-58.

24. H. Wang and J. A. Joseph, Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader, Free Rad. Biol. Med. 27 (1999) 612-616; DOI: 10.1016/s0891-5849(99) 00107-0.

25. N. P. Seeram, Y. J. Zhang and M. G. Nair, Inhibition of proliferation of human cancer cells and cyclooxygenase enzymes by anthocyanidins and catechins, Nutr. Cancer 46 (2003) 101-106; DOI: 10.1207/s15327914nc4601_13.

26. G. Liang, A. Z. Tang, X. Z. Lin, L. Li, S. Zhang, Z. Huang, H. Tang and Q. Q. Li, Green tea catechins augment the antitumor activity of doxorubicin in an in vivo mouse model for chemoresistant liver cancer, Int. J. Oncol. 37 (2010) 111-123; DOI: 10.3892/ijo_00000659.

27. G. W. Dryden, A. Lam, K. Beatty, H. H. Qazzaz and C. J. McClain, A pilot study to evaluate the safety and efficacy of an oral dose of (-)-epigallocatechin-3-gallate-rich polyphenon E in patients with mild to moderate ulcerative colitis, Inflamm. Bowel Dis. 19 (2013) 1904-1912; DOI: 10.1097/MIB.0b013e31828f5198.

28. H. H. Chow, I. A. Hakim, D. R. Vining, J. A. Crowell, J. Ranger-Moore, W. M. Chew, C. A. Celaya, S. R. Rodney, Y. Hara and D. S. Alberts, Effects of dosing condition on the oral bioavailability of green tea catechins after single-dose administration of Polyphenon E in healthy individuals, Clin. Cancer Res. 11 (2005) 4627-4633; DOI: 10.1158/1078-0432.CCR-04-2549.

29. G. Stammler and M. Volm, Green tea catechins (EGCG and EGC) have modulating effects on the activity of doxorubicin in drug-resistant cell lines, Anti-cancer Drugs 8 (1997) 265-268.

30. G. Mazzanti, F. Menniti-Ippolito, P. A. Moro, F. Cassetti, R. Raschetti, C. Santuccio and S. Mastrangelo, Hepatotoxicity from green tea: a review of the literature and two unpublished cases, Eur. J. Clin. Pharmacol. 65 (2009) 331-341; DOI: 10.1007/s00228-008-0610-7

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