A major constituent of green tea, EGCG, inhibits the growth of a human cervical cancer cell line, CaSki cells, through apoptosis, G1 arrest, and regulation of gene expression

被引:116
作者
Ahn, WS
Huh, SW
Bae, SM
Lee, IP
Lee, JM
Namkoong, SE
Kim, CK
Sin, JI
机构
[1] Catholic Univ Korea, Ctr Canc Res 6004 2, Catholic Res Inst Med Sci, Coll Med, Seoul 137040, South Korea
[2] Catholic Univ Korea, Dept Obstet & Gynecol, Coll Med, Seoul 137040, South Korea
[3] Seoul Natl Univ, Coll Pharm, Seoul, South Korea
关键词
D O I
10.1089/104454903321655846
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
A constituent of green tea, (2)-epigallocatechin-3-gallate (EGCG) has been known to possess antiproliferative properties. In this study, we investigated the anticancer effects of EGCG in human papillomavirus (HPV)-16 associated cervical cancer cell line, CaSki cells. The growth inhibitory mechanism(s) and regulation of gene expression by EGCG were also evaluated. EGCG showed growth inhibitory effects in CaSki cells in a dose-dependent fashion, with an inhibitory dose (ID)(50) of approximately 35 muM. When CaSki cells were further tested for EGCG-induced apoptosis, apoptotic cells were significantly observed after 24 h at 100 muM EGCG. In contrast, an insignificant induction of apoptotic cells was observed at 35 muM EGCG. However, cell cycles at the G1 phase were arrested at 35 muM EGCG, suggesting that cell cycle arrests might precede apoptosis. When CaSki cells were tested for their gene expression using 384 cDNA microarray, an alteration in the gene expression was observed by EGCG treatment. EGCG downregulated the expression of 16 genes over time more than twofold. In contrast, EGCG upregulated the expression of four genes more than twofold, suggesting a possible gene regulatory role of EGCG. This data supports that EGCG can inhibit cervical cancer cell growth through induction of apoptosis and cell cycle arrest as well as regulation of gene expression in vitro. Furthermore, in vivo antitumor effects of EGCG were also observed. Thus, EGCG likely provides an additional option for a new and potential drug approach for cervical cancer patients.
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页码:217 / 224
页数:8
相关论文
共 39 条
[1]
Cell cycle dysregulation by green tea polyphenol epigallocatechin-3-gallate [J].
Ahmad, N ;
Cheng, PY ;
Mukhtar, H .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 275 (02) :328-334
[2]
Role of the retinoblastoma (pRb)-E2F/DP pathway in cancer chemopreventive effects of green tea polyphenol epigallocatechin-3-gallate [J].
Ahmad, N ;
Adhami, VM ;
Gupta, S ;
Cheng, PY ;
Mukhtar, H .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2002, 398 (01) :125-131
[3]
Green tea constituent epigallocatechin-3-gallate and induction of apoptosis and cell cycle arrest in human carcinoma cells [J].
Ahmad, N ;
Feyes, DK ;
Nieminen, AL ;
Agarwal, R ;
Mukhtar, H .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1997, 89 (24) :1881-1886
[4]
Effect of (-)-epigallocatechin gallate on leukemic blast cells from patients with acute myeloblastic leukemia [J].
Asano, Y ;
Okamura, S ;
Ogo, T ;
Eto, T ;
Otsuka, T ;
Niho, Y .
LIFE SCIENCES, 1996, 60 (02) :135-142
[5]
Green tea constituent (-)-epigallocatechin-3-gallate inhibits topoisomerase I activity in human colon carcinoma cells [J].
Berger, SJ ;
Gupta, S ;
Belfi, CA ;
Gosky, DM ;
Mukhtar, H .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 288 (01) :101-105
[6]
THE EFFECTS OF CHINESE TEA ON THE OCCURRENCE OF ESOPHAGEAL TUMORS INDUCED BY N-NITROSOMETHYLBENZYLAMINE IN RATS [J].
CHEN, JS .
PREVENTIVE MEDICINE, 1992, 21 (03) :385-391
[7]
Green tea epigallocatechin gallate shows a pronounced growth inhibitory effect on cancerous cells but not on their normal counterparts [J].
Chen, ZP ;
Schell, JB ;
Ho, CT ;
Chen, KY .
CANCER LETTERS, 1998, 129 (02) :173-179
[8]
Regulation of transcription by proteins that control the cell cycle [J].
Dynlacht, BD .
NATURE, 1997, 389 (6647) :149-152
[9]
GREEN TEA COMPOSITION, CONSUMPTION, AND POLYPHENOL CHEMISTRY [J].
GRAHAM, HN .
PREVENTIVE MEDICINE, 1992, 21 (03) :334-350
[10]
Why drinking green tea could prevent cancer [J].
Jankun, J ;
Selman, SH ;
Swiercz, R ;
SkrzypczakJankun, E .
NATURE, 1997, 387 (6633) :561-561