(-)-Epigallocatechin-3-gallate 藉由抑制基本表現及第六白介素誘導之訊息傳遞及轉錄因子3路徑誘發頭頸部腫瘤細胞凋亡

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Many beneficial properties have been attributed to (-)-epigallocatechin-3-gallate (EGCG), including chemopreventive, anticarcinogenic, and antioxidant active. The antitumor effect of green tea compound EGCG have not been studied clearly in head and neck squamous cell carcinoma cells. Previous study indicated that the constitutive activation of singal-transducer-and-activator-3 (STAT3) were associated with the proliferation of HNSCC cells. Numerous reports suggest that interleukin-6 (IL-6) promotes survival and proliferation of tumor cells through the phosphorylation of STAT3. Constitutive of STAT3 in HNSCC was relative with its proliferation and survival. Thus, compound that can suppress STAT3 activation have potential for the treatment of HNSCC. Therefore, we examined in detail the molecular effect of EGCG on four HNSCC cell lines, SAS, Cal-27, Ca9-22 and HSC3. In the beginning, we found the great inhibition on HNSCC cells of EGCG. Further, we focused the effect of EGCG on STAT3 signal pathway. In this study, the 70% lethal dose (IC70) of EGCG for three cell lines, SAS, Cal-27 and Ca9-22, was 20 μM, and EGCG inhibited STAT3 phosphorylation in a dose- and time- dependent manner. Nuclear translocation of STAT3 was also inhibited by EGCG. Besides inhibiting constitutive expression, EGCG also abrogated the IL-6-induced activation of STAT3 and further inhibited IL-6-induced proliferation on HNSCC cell. Compare with Apigenin, Curcumin and AG490, EGCG was more effective inhibitor of IL-6-induced proliferation on HNSCC cells. Overall, our results strongly suggest that EGCG is a potent inhibitor of constitutive and IL-6-induced STAT3 phosphorylation. This mechanism may be at least partially responsible for EGCG’s ability to suppress proliferation of HNSCC cells. Taken together, these finding suggest that this naturally occurring compound may be useful, in the chemoprevention and/or treatment of HNSCC.