Green tea catechin, epigallocatechin‑3‑gallate, attenuates the cell viability of human non‑small‑cell lung cancer A549 cells via reducing Bcl‑xL expression

Sonoda,Jun‑Ichiro; Ikeda,Ryuji; Baba,Yasutaka; Narumi,Keiko; Kawachi,Akio; Tomishige,Erisa; Nishihara,Kazuya; Takeda,Yasuo; Yamada,Katsushi; Sato,Keizo; Motoya,Toshiro

doi:10.3892/etm.2014.1719

Green tea catechin, epigallocatechin‑3‑gallate, attenuates the cell viability of human non‑small‑cell lung cancer A549 cells via reducing Bcl‑xL expression

Authors:
- Jun‑Ichiro Sonoda
- Ryuji Ikeda
- Yasutaka Baba
- Keiko Narumi
- Akio Kawachi
- Erisa Tomishige
- Kazuya Nishihara
- Yasuo Takeda
- Katsushi Yamada
- Keizo Sato
- Toshiro Motoya
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Affiliations: First Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kyushu University of Health & Welfare, Nobeoka, Miyazaki 882‑8508, Japan, Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka, Kagoshima 890‑8520, Japan, Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka, Kagoshima 890‑8520, Japan, First Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kyushu University of Health & Welfare, Nobeoka, Miyazaki 882‑8508, Japan, Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka, Kagoshima 890‑8520, Japan, Department of Clinical Pharmacology, Faculty of Pharmaceutical Science, Nagasaki International University, Sasebo, Nagasaki 859‑3298, Japan, Department of Clinical Biochemistry, School of Pharmaceutical Sciences, Kyushu University of Health & Welfare, Nobeoka, Miyazaki 882‑8508, Japan
Published online on: May 19, 2014 https://doi.org/10.3892/etm.2014.1719
Pages: 59-63

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Abstract

Clinical and epidemiological studies have indicated that the consumption of green tea has a number of beneficial effects on health. Epigallocatechin‑3‑gallate (EGCg), the major polyphenolic compound present in green tea, has received much attention as an active ingredient. Among the numerous promising profiles of EGCg, the present study focused on the anticancer effects. Apoptosis induced by EGCg and subsequent cell growth suppression have been demonstrated in a number of cell culture studies. However, the underlying mechanism of apoptotic cell death remains unclear. Thus, the aim of the present study was to identify the major molecule that mediates proapoptotic cell death by EGCg. The effect of EGCg on cell proliferation and the induction of mRNA that modulates apoptotic cell death was evaluated in the A549 human non‑small‑cell lung cancer cell line. In addition, morphological changes were assessed by microscopy in A549 cells that had been treated with 100 µM EGCg for 24 h. The MTT assay revealed that cell proliferation was significantly reduced by EGCg in a dose‑dependent manner (3‑100 µM). The mRNA expression level of B‑cell lymphoma‑extra large (Bcl‑xL) was decreased in A549 cells following 24 h incubation with 100 µM EGCg. Therefore, the results indicated that the inhibition of cell proliferation by EGCg may be achieved via suppressing the expression of the cell death‑inhibiting gene, Bcl‑xL.

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1	Baba Y, Sonoda JI, Hayashi S, et al: Reduction of oxidative stress in liver cancer patients by oral green tea polyphenol tablets during hepatic arterial infusion chemotherapy. Exp Ther Med. 4:452–458. 2012.PubMed/NCBI
2	Lee IP, Kim YH, Kang MH, et al: Chemopreventive effect of green tea (Camellia sinensis) against cigarette smoke-induced mutations (SCE) in humans. J Cell Biochem Suppl. 27:68–75. 1997.
3	Shimizu M, Fukutomi Y, Ninomiya M, et al: Green tea extracts for the prevention of metachronous colorectal adenomas: a pilot study. Cancer Epidemiol Biomarkers Prev. 17:3020–3025. 2008. View Article : Google Scholar : PubMed/NCBI
4	Khan N, Adhami VM and Mukhtar H: Review: green tea polyphenols in chemoprevention of prostate cancer: preclinical and clinical studies. Nutr Cancer. 61:836–841. 2009. View Article : Google Scholar : PubMed/NCBI
5	Suganuma M, Saha A and Fujiki H: New cancer treatment strategy using combination of green tea catechins and anticancer drugs. Cancer Sci. 102:317–323. 2011. View Article : Google Scholar : PubMed/NCBI
6	Imai K, Suga K and Nakachi K: Cancer-preventive effects of drinking green tea among a Japanese population. Prev Med. 26:769–775. 1997. View Article : Google Scholar : PubMed/NCBI
7	Inoue M, Tajima K, Mizutani M, et al: Regular consumption of green tea and the risk of breast cancer recurrence: follow-up study from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan. Cancer Lett. 167:175–182. 2001. View Article : Google Scholar
8	Bettuzzi S, Brausi M, Rizzi F, et al: Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. Cancer Res. 66:1234–1240. 2006.
9	Naganuma T, Kuriyama S, Kakizaki M, et al: Green tea consumption and hematologic malignancies in Japan: the Ohsaki study. Am J Epidemiol. 170:730–738. 2009. View Article : Google Scholar : PubMed/NCBI
10	Nishikawa T, Nakajima T, Moriguchi M, et al: A green tea polyphenol, epigalocatechin-3-gallate, induces apoptosis of human hepatocellular carcinoma, possibly through inhibition of Bcl-2 family proteins. J Hepatol. 44:1074–1082. 2006. View Article : Google Scholar
11	Yamauchi R, Sasaki K and Yoshida K: Identification of epigallocatechin-3-gallate in green tea polyphenols as a potent inducer of p53-dependent apoptosis in the human lung cancer cell line A549. Toxicol In Vitro. 23:834–839. 2009. View Article : Google Scholar : PubMed/NCBI
12	Li HC, Yashiki S, Sonoda J, et al: Green tea polyphenols induce apoptosis in vitro in peripheral blood T lymphocytes of adult T-cell leukemia patients. Jap J Cancer Res. 91:34–40. 2000. View Article : Google Scholar : PubMed/NCBI
13	Tsukahara T, Kannagi M, Ohashi T, et al: Induction of Bcl-x(L) expression by human T-cell leukemia virus type 1 Tax through NF-kappaB in apoptosis-resistant T-cell transfectants with Tax. J Virol. 73:7981–7987. 1999.PubMed/NCBI
14	Ahmad N, Gupta S and Mukhtar H: Green tea polyphenol epigallocatechin-3-gallate differentially modulates nuclear factor κB in cancer cells versus normal cells. Arch Biochem Biophys. 376:338–346. 2000.PubMed/NCBI
15	Sonoda J, Koriyama C, Yamamoto S, et al: HTLV-1 provirus load in peripheral blood lymphocytes of HTLV-1 carriers is diminished by green tea drinking. Cancer Sci. 95:596–601. 2004. View Article : Google Scholar : PubMed/NCBI
16	Khoshnan A, Tindell C, Laux I, et al: The NF-kappa B cascade is important in Bcl-xL expression and for the anti-apoptotic effects of the CD28 receptor in primary human CD4+ lymphocytes. J Immunol. 165:1743–1754. 2000.PubMed/NCBI
17	Bui NT, Livolsi A, Peyron JF and Prehn JH: Activation of nuclear factor kappaB and Bcl-x survival gene expression by nerve growth factor requires tyrosine phosphorylation of IkappaBalpha. J Cell Bio. 152:753–764. 2001. View Article : Google Scholar : PubMed/NCBI
18	Carmichael J, De Graff WG, Gazdar AF, Minna JD and Mitchell JB: Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Res. 47:936–942. 1987.PubMed/NCBI
19	Cabrera C, Artacho R and Giménez R: Beneficial effects of green tea - a review. J Am Coll Nutr. 25:79–99. 2006. View Article : Google Scholar
20	Yamamoto T, Staples J, Wataha J, et al: Protective effects of EGCG on salivary gland cells treated with gamma-radiation or cis-platinum(II)diammine dichloride. Anticancer Res. 24:3065–3073. 2004.PubMed/NCBI
21	Zheng J, Lee HC, Bin Sattar MM, Huang Y and Bian JS: Cardioprotective effects of epigallocatechin-3-gallate against doxorubicin-induced cardiomyocyte injury. Eur J Pharmacol. 652:82–88. 2011. View Article : Google Scholar : PubMed/NCBI
22	Ohe Y, Ohashi Y, Kubota K, et al: Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: Four-Arm Cooperative Study in Japan. Ann Oncol. 18:317–323. 2007. View Article : Google Scholar : PubMed/NCBI
23	Liang G, Tang A, Lin X, et al: Green tea catechins augment the antitumor activity of doxorubicin in an in vivo mouse model for chemoresistant liver cancer. Int J Oncol. 37:111–123. 2010.PubMed/NCBI
24	Kurahashi N1, Sasazuki S, Iwasaki M, Inoue M and Tsugane S; JPHC Study Group. Green tea consumption and prostate cancer risk in Japanese men: a prospective study. Am J Epidemiol. 167:71–77. 2008. View Article : Google Scholar : PubMed/NCBI
25	Paschka AG, Butler R and Young CY: Induction of apoptosis in prostate cancer cell lines by the green tea component, (−)-epigallocatechin-3-gallate. Cancer Lett. 130:1–7. 1998.
26	Fujiki H: Two stages of cancer prevention with green tea. J Cancer Res Clin Oncol. 125:589–597. 1999. View Article : Google Scholar : PubMed/NCBI
27	Inoue M, Tajima K, Mizutani M, Iwata H, Iwase T, Miura S, Hirose K, Hamajima N and Tominaga S: Regular consumption of green tea and the risk of breast cancer recurrence: follow-up study from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan. Cancer Lett. 167:175–182. 2001. View Article : Google Scholar
28	Orner GA, Dashwood WM, Blum CA, Díaz GD, Li Q and Dashwood RH: Suppression of tumorigenesis in the Apc(min) mouse: down-regulation of beta-catenin signaling by a combination of tea plus sulindac. Carcinogenesis. 24:263–267. 2003. View Article : Google Scholar : PubMed/NCBI
29	Gao YT, McLaughlin JK, Blot WJ, Ji BT, Dai Q and Fraumeni JF Jr: Reduced risk of esophageal cancer associated with green tea consumption. J Natl Cancer Inst. 86:855–858. 1994. View Article : Google Scholar : PubMed/NCBI
30	Hibasami H, Komiya T, Achiwa Y, Ohnishi K, Kojima T, Nakanishi K, Akashi K and Hara Y: Induction of apoptosis in human stomach cancer cells by green tea catechins. Oncol Rep. 5:527–529. 1998.PubMed/NCBI
31	Takada M, Nakamura Y, Koizumi T, Toyama H, Kamigaki T, Suzuki Y, Takeyama Y and Kuroda Y: Suppression of human pancreatic carcinoma cell growth and invasion by epigallocatechin-3-gallate. Pancreas. 25:45–48. 2002. View Article : Google Scholar : PubMed/NCBI
32	Fujimoto N, Sueoka N, Sueoka E, Okabe S, Suganuma M, Harada M and Fujiki H: Lung cancer prevention with (−)-epigallocatechin gallate using monitoring by heterogeneous nuclear ribonucleoprotein B1. Int J Oncol. 20:1233–1239. 2002.
33	Okabe S, Suganuma M, Hayashi M, Sueoka E, Komori A and Fujiki H: Mechanisms of growth inhibition of human lung cancer cell line, PC-9, by tea polyphenols. Jap J Cancer Res. 88:639–643. 1997. View Article : Google Scholar : PubMed/NCBI
34	Lee MH, Han DW, Hyon SH and Park JC: Apoptosis of human fibrosarcoma HT-1080 cells by epigallocatechin-3-O-gallate via induction of p53 and caspases as well as suppression of Bcl-2 and phosphorylated nuclear factor-κB. Apoptosis. 16:75–85. 2011.PubMed/NCBI
35	Hong J, Lambert JD, Lee SH, Sinko PJ and Yang CS: Involvement of multidrug resistance-associated proteins in regulating cellular levels of (−)-epigallocatechin-3-gallate and its methyl metabolites. Biochem Biophys Res Commun. 310:222–227. 2003.
36	Ahn SC, Kim GY, Kim JH, et al: Epigallocatechin-3-gallate, constituent of green tea, suppresses the LPS-induced phenotypic and functional maturation of murine dendritic cells through inhibition of mitogen-activated protein kinases and NF-kappaB. Biochem Biophys Res Commun. 313:148–155. 2004. View Article : Google Scholar
37	Lee HH, Dadgostar H, Cheng Q, Shu J and Cheng G: NF-kappaB-mediated up-regulation of Bcl-x and Bfl-1/A1 is required for CD40 survival signaling in B lymphocytes. Proc Natl Acad Sci U S A. 96:9136–9141. 1999. View Article : Google Scholar : PubMed/NCBI