| Summary: | 碩士 === 中山醫學大學 === 醫學分子毒理學研究所 === 95 === Many clinically successful anticancer drugs are themselves either natural products or have been developed from Chinese herbs. Chalcones are the intermediate precursors for all flavonoids. Chalcones and their derivatives have been shown to possess a wide range of biological functions including anti-inflammatory, anti-bacterial, anti-malarial, anti-cancer. We found 2’-Hydroxy-2, 3, 4’, 6’-tetramethoxychalcone is preferentially toxic to cancer cell lines in comparison with normal lung cell lines. Previous studies have suggested that the loss of telomerase activity is a favotable prognostic marker. Therefore, telomerase has become an attractive target for anti-cancer therapeutic interventions. In this study, we demonstrated that 2’-Hydroxy-2, 3, 4’, 6’-tetramethoxychalcone suppressed telomerase activity expression in A549 cells. 2’-Hydroxy-2, 3, 4’, 6’-tetramethoxychalcone also repressed hTERT promoter activity, resulted in decreased hTERT mRNA expression. Treatment of intracellular calcium chelator BAPTA-AM neutralized the inhibitory effect of 2’-Hydroxy-2, 3, 4’, 6’-tetramethoxychalcone on telomerase activity. Using Fluo-3AM for Ca2+ detection, we proved that 2’-Hydroxy-2, 3, 4’, 6’-tetramethoxychalcone induced increased intensity of intracellular calcium signals. These data indicate that calcium might participate in the suppression of telomerase activity. In addition, we also evaluated the effect of chalcone, flavonoid and isoflavonoid derivatives on A549 cell migration by Boyden chamber, gelatin zymography and wound healing, however, no inhibitory effect on cell migration was observed. Finally, the anti-tumor growth effect of 2’-Hydroxy-2, 3, 4’, 6’-tetramethoxychalcone was evident in its inhibitory growth of lung tumor A549 cells in nude mice model and in soft agar, chalcone derivative 2’-Hydroxy-2, 3, 4’, 6’-tetramethoxychalcone inhibits telomerase activity in lung cancer cells and tumor growth, provides a rationale for the further development of this class of compounds as novel cancer chemotherapeutic agents.
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