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

Abstract

A constituent of green tea, (-)-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 microM. When CaSki cells were further tested for EGCG-induced apoptosis, apoptotic cells were significantly observed after 24 h at 100 microM EGCG. In contrast, an insignificant induction of apoptotic cells was observed at 35 microM EGCG. However, cell cycles at the G1 phase were arrested at 35 microM 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.

Epigallocatechin-3-gallate (EGCG): Chemical and biomedical perspectives

“…Spurred by previous results that indicated EGCG could inhibit cervical cancer cell growth in vitro through the regulation of gene expression, cell cycle progression, and apoptosis (Ahn et al, 2003a), Ahn and coworkers (2003b) investigated the clinical efficacy of various EGCG and green tea preparations on human cervical lesions. A total of ninety women with human papilloma virus (HPV) infected cervical lesions were divided into four treatment groups and one control group.…”

Green tea catechins for treatment of external genital warts

“…In addition to possessing antiviral [6][7][8] and immunostimulatory [9][10][11][12] properties, catechins also exhibit antitumor [13][14][15][16] and antioxidative 11,17 effects. There is also sufficient evidence for antiangiogenic activity.…”

“…However, catechins induce the release of many immune stimulatory interleukins while at the same time suppressing the release of immune inhibitory interleukins. 9,10 Specifically, catechins activate T lymphocytes, induce the release of both tumor necrosis factoralpha (TNF-␣) and interferon-gamma (IFN-␥), and stimulate macrophages to release immune stimulatory cytokines. This promotes recruitment of monocytes, dendritic cells, lymphocytes, natural killer cells, and T-helper cells to aid in the immune response (Figure 3).…”

Specific killing of multiple myeloma cells by (-)-epigallocatechin-3-gallate extracted from green tea: biologic activity and therapeutic implications

“…18,19 In prostate carcinoma cells (LNcaP), EGCG induces apoptosis by activation of p53 and p14ARF-mediated suppression of MDM2. In this study we have demonstrated that EGCG induces apoptotic cell death in multiple myeloma (MM) cells including IL-6-dependent cells and primary MM cells in vitro, while having no significant effect on growth of normal cells (peripheral blood mononuclear cells [PBMCs] and fibroblasts), and induces apoptosis and inhibition of growth in vivo in a murine model of human MM.…”