(-)-Epigallocatechin-3-gallate induces apoptosis in gastric cancer cell lines by down-regulating survivin expression

Abstract

Abstract. The polyphenol (-)-epigallocatechin-3-gallate (EGCG) is a green tea constituent, which has been shown to inhibit cancer cell growth in vitro, in vivo and in epidemiological studies. In this study, we investigated its effects in gastric cancer cell lines. Five gastric cancer cell lines, the MKN-1, MKN-28, MKN-45, NUGC-3 and TMK-1, were found to be sensitive to EGCG treatment. Of all the cell lines tested, NUGC-3 was the most sensitive. EGCG treatment of NUGC-3 cells induced apoptosis, which was confirmed by sub-G1 analysis, caspase-Glo assay and Western blotting against cleaved PARP and cleaved caspase-3. EGCG treatment lowered survivin and increased Bax and TRAIL expression. Furthermore, EGCG induced p73 activation in NUGC-3 cells. Small interfering RNA against p73 diminished EGCG effects on survivin expression and cell viability. These results show that EGCG induces cell death in gastric cancer cells by apoptosis via inhibition of survivin expression downstream of p73. This study provides a novel mechanism whereby EGCG potentially inhibits cancer cell growth, concluding that EGCG may be a potential candidate in anti-survivin cancer therapy.

Natural Polyphenols for Prevention and Treatment of Cancer

“…While at higher concentration (>20 μM), it exhibited anti-proliferation activities through induction of G 2 /M cell cycle arrest but not apoptosis [44]. Another study found that several gastric cancer cell lines were sensitive to EGCG (100 μM) induced apoptosis due to inhibition of survivin, a potent anti-apoptotic protein [45]. Many signaling pathways might be affected by EGCG treatment.…”

The Antiproliferative Effect of Chakasaponins I and II, Floratheasaponin A, and Epigallocatechin 3-O-Gallate Isolated from Camellia sinensis on Human Digestive Tract Carcinoma Cell Lines

“…There are conflicting reports of apoptotic and nonapoptotic cell death induced by compound 4 , and the exact molecular mechanisms have not been fully elucidated yet. However, most of the previous reports have concluded that this compound induces caspase-mediated apoptosis in various tumor cells via the mitochondrial pathway [44,45] or via the death receptor [46,47,48]. Conversely, several reports demonstrated the involvement of nonapoptotic cell death, such as caspase-independent necrosis-like cell death [49] or reactive oxygen species (ROS)-mediated lysosomal membrane permeabilization [50].…”

(-)-Epigallocatechin-3-gallate Modulates the Differential Expression of Survivin Splice Variants and Protects Spermatogenesis During Testicular Torsion

“…EGCG is recognized as a chemopreventive agent, which is inversely correlated with the prevalence of various cancer types, including breast, prostatic, colonic, mammary, ovarian and pancreatic cancers [37-39]. In most of these cancers, survivin has been shown to be a molecular target of EGCG, in which increased survivin levels are suppressed by EGCG treatment [40-42]. Nonetheless, in non-cancer diseases, the relationship between EGCG and the expression of survivin splice variants has not been reported prior to this study.…”