Assessment Synergistic Effects of Integrated Therapy with Epigallocatechin-3-Gallate (EGCG) & Arsenic Trioxide and Irradiation on Breast Cancer Cell Line

  • Vahid CHANGIZI Department of Technology of Radiology and Radiotherapy, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
  • Samayeh AZARIASL Mail Department of Technology of Radiology and Radiotherapy, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
  • Elahe MOTEVASELI Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  • Saeedeh JAFARI NODOOSHAN School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
Epigallocatechin-3-gallate;, Arsenic trioxide;, Apoptosis


Background: Breast cancer is the most common invasive malignancy among women in the world. The current breast cancer therapies pose significant clinical challenges. Low-dose chemotherapy represents a new strategy to treat solid tumors in combination with natural products such as green tea catechins. Epigallocatechin-3-gallate (EGCG) is the major polyphenolic extract from green tea with potent anticancer and antioxidant effects. The purpose of this study was to investigate the effects of EGCG, Arsenic trioxide (ATO) and gamma radiation on MCF-7 cell line.

Methods: The anti-proliferative effects of EGCG and ATO individually, moreover in combination with radiation on MCF-7 cells were evaluated with MTT assay. The expression of apoptotic gens (Bax, Bcl-2, Caspase-3 and Fas) was assessed by real-time PCR.

Results: Based on the results of MTT assay, EGCG and ATO exhibited dose and time-dependent anti-proliferative effects on MCF-7 cells. The combined therapy of EGCG and ATO in presence and absence radiation could rise cell death up to 80%. Moreover, integrated therapy made Bax up-regulated and Bcl-2 down-regulated.

Conclusion: In assessment synergistic effects of integrated therapy with EGCG and ATO and irradiation had been significant impact on low dose chemotherapy for breast cancer treatment.


1. Siegel R, Ward E, Brawley O, Jemal A (2011). The impact of eliminating socio-economic and racial disparities on prema-ture cancer deaths. CA Cancer J Clin, 61(4):212-36.
2. Gangopadhyay S, Nandy P, Mukhopadhyay H (2013). Breast cancer stem cells and atherapeutic target. Clin Breast Cancer, 13: 7-15.
3. Ghoncheh M, Pournamdar Z, Salehiniya H (2016). The incidence and mortality and epidemiology of breast cancer in the world. Asian Pac J Cancer Prev, 17(3): 43-46.
4. Fouladi N, Amani F, Harghi A, Nayebyazdi N (2011). Five year survival of women with breast cancer in Ardabil, north-west of Iran. Asian Pac J Cancer Prev, 12 (7):1799-801.
5. Mousavi SM, Gouya MM, Ramazani R, et al (2009). Cancer incidence and mortality in Iran. Ann Oncol, 20(3):556-563.
6. Li C, Malone K, Daling J (2003). Differ-ences in breast cancer stage, treatment, and survival by race and ethnicity. Arch Intern Med, 163(1): 49-56.
7. McLaughlin N, Annabi B, Bouzeghrane M, et al (2006). The survivinmediated radio-resistant phenotype of glioblastomas is regulated by Rhoa and inhibited by the green tea polyphenol epigallocatechin-3-gallate. Brain Res, 1071(1):1-9.
8. Lu G, Liao J, Yang G, et al (2006). Inhibi-tion of adenoma progression to adeno-carcinoma in adenocarcinoma in a 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis model in A/J mice by tea polyphenols and caffeine.Cancer Res, 66 (23):11494-501.
9. Thangapazham R, Singh A, Sharma A, et al (2007). Green tea polyphenols and its constituent epigallocatechin gallate inhib-its proliferation of human breast cancer cells in vitro and in vivo. Cancer Lett, 245(1-2): 232-41.
10. Yang C, Wang X, Lu G, Picinich S (2009).Cancer prevention by tea: Animal studies, molecular mechanisms and hu-man relevance. Nat Rev Cancer, 9(6): 429-39.
11. Yang C, Wang H, Li G, et al (2011). Cancer prevention by tea: Evidence from labora-tory studies. Pharmacol Res, 64:113-22.
12. Singh B, Shankar S, Srivastava R (2011). Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspec-tives and clinical applications. Biochem Pharmacol, 82(12):1807-1821.
13. Lecumberri E, Dupertuis Y, Miralbell R, Pichard C (2013). Green tea polyphenol epigallocatechin-3-gallate (EGCG) as ad-juvant in cancer therapy. Clin Nutr, 32(6):894-903.
14. Wessner B, Strasser E, Koitz N, et al (2007). Green tea polyphenol administration partly ameliorates chemotherapyinduced side effects in the small intestine of mice. J Nutr, 137(3):634-40.
15. Suganuma M, Saha A, Fujiki H (2011). New cancer treatment strategy using combina-tion of green tea catechins and anticancer drugs. Cancer Sci, 102(2):317-23.
16. Kwong Y, Todd D (1997). Delicious poi-son: arsenic trioxide for the treatment of leukemia. Blood. 89(9):3487-8.
17. Ye J, Li A, Liu Q, et al (2005). Inhibition of mitogen‐activated protein kinase kinase enhances apoptosis induced by arsenic trioxide in human breast cancer MCF‐7 cells. Clin Exp Pharmacol Physiol, 32(12):1042-8.
18. Bartelink H, Horiot J-C, Poortmans P, et al (2001). Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation. N Engl J Med, 345(19):1378-87.
19. Wernicke A, Shamis M, Sidhu K, et al (2013). Complication Rates in patients with negatve axillary nodes 10-years after local breast radiotherapy following either sentinel lymph node dissection or axillary clearance. Am J Clin Oncol, 36(1):12-19.
20. Taylor R, Cullen S, Martin S (2008). Apopto-sis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol, 9(3): 231-41.
21. Ouyang L, Shi Z, Zhao S, et al (2012). Pro-grammed cell death pathways in cancer: a review of apoptosis, autophagy and pro-grammed necrosis. Cell Prolif, 45(6): 487-98.
22. Rai NK, Tripathi K, Sharma D, Shukla VK (2005). Apoptosis: a basic physiologic process in wound healing. Int J Low Ex-trem Wounds, 4(3):138-44.
23. Schmittgen T, Livak K (2008). Analyzing re-al-time PCR data by the comparative CT method. Nat Protoc, 3(6):1101-8.
24. Hsieh T, Wu J (2008). Suppression of cell proliferation and gene expression by combinatorial synergy of EGCG, resveratrol and gamma-tocotrienol in es-trogen receptor-positive MCF-7 breast cancer cells. Int J Oncol, 33:851-9.
25. Farabegoli F, Papi A, Bartolini G, et al (2010).(-)-Epigallocatechin-3-gallate downregulates Pg-P and BCRP in a ta-moxifen resistant MCF-7cell line. Phyto-medicine, 17(5):356-62.
26. Sakata M, Ikeda T, Imoto S, et al (2011). Prevention of mammary carcinogenesis in C3H/OUJ mice by green tea and ta-moxifen. Asian Pac J Cancer Prev, 12(2): 567-71.
27. Fujiki H, Sueoka E, Watanabe T, Suganuma M (2015). Synergistic enhancement of an-ticancer effects on numerous human can-cer cell lines treated with the combination of EGCG, other green tea catechins, and anticancer compounds. J Cancer Res Clin Oncol, 141(9):1511–22.
28. Chen D, Wan H, Yang J, et al (2011). EGCG, green tea polyphenols and their synthetic analogs and prodrugs for hu-man cancer prevention and treatment. Adv Clin Chem, 53: 155-177.
29. Kim JW, Amin AR, Shin DM (2010). Chemoprevention of head and neck can-cer with green tea polyphenols. Cancer Prev Res(Phila), 3: 900-909.
30. Chang Lee T, Cheng Cheng I, Jie Shue J, Wang TC (2011). Cytotoxicity of arsenic trioxide is enhanced by (−)-epigallocatechin-3-gallate via suppression of ferritin in cancer cells. Toxicol Appl Pharmacol, 250:69-77.
31. Ashkenazi A (2008). Targeting the extrinsic apoptosis pathway in cancer. Cytokine Growth Factor Rev, 19(3-4): 325-31.
32. Zhang G, Wang Y, Zhang Y, et al (2012). Anti-Cancer Activities of Tea Epigallocat-echin-3-Gallate in Breast Cancer Patients under Radiotherapy. Curr Mol Med, 12(2):163–76.
33. Baj G, Arnulfo A, Deaglio S, et al (2002). Arsenic trioxide and breast cancer: analy-sis of the apoptotic, differentiative and immunomodulatory effects. Breast Cancer Res Treat, 73 (1):61-73.
How to Cite
CHANGIZI V, AZARIASL S, MOTEVASELI E, JAFARI NODOOSHAN S. Assessment Synergistic Effects of Integrated Therapy with Epigallocatechin-3-Gallate (EGCG) & Arsenic Trioxide and Irradiation on Breast Cancer Cell Line. Iran J Public Health. 49(8):1555-1563.
Original Article(s)