香茹增加TRAIL 誘發肝癌細胞凋亡與c-FLIP 表現降低有關

Glossogyne Tenuifolia Enhances TRAIL-induced Apoptosis in Hepatoma Involving Down Regulation of c-FLIP

香茹 （Glossogyne tenuifolia） 為澎湖特有的草藥，近年的研究顯示香茹具有抗發炎、降低B型肝炎病毒表面抗原表現及抑制癌細胞增殖等功效。腫瘤壞死因子相關的凋亡誘導蛋白 （Tumornecrosis factor-related apoptosis inducing ligand, TRAIL） 會造成腫瘤細胞的凋亡，但對正常細胞並不具有毒性。本研究目的在了解香茹是否輔助TRAIL 誘發肝癌細胞凋亡並探討其作用機轉。研究結果顯示香茹乙酸乙酯層 （GT/EA） 可以有效的增加TRAIL 誘發肝癌細胞株 （Hep 3B） 凋亡。利用西方墨點法檢測，發現GT/EA 會促使裁切型ADP- 核酸聚合酶 （Poly （ADP-ribose） polymerase-1,PARP-1） 蛋白質片段大量增加。而細胞型類FLICE 抑制蛋白 （cellular FLICE-like inhibitory protein,c-FLIP）是死亡受器誘發細胞凋亡過程中主要的抑制性蛋白質，結果顯示Hep 3B在GT/EA作用下，c-FLIP 表現量降低。本研究發現香茹具有提升肝癌細胞對TRAIL 敏感度的能力，與c-FLIP 表現降低相關聯，因此促進TRAIL 誘發Hep 3B 的細胞凋亡。

Glossogyne tenuifolia (Hsiang-Ju) is a unique traditional herb medicine in Penghu Islands. It was reported that the extract exhibited the anti-inflammation, reduction of surface antigen of HBV and proliferation inhibition of cancer cells. Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) could trigger apoptosis specific in cancer cells but not normal cells. In this study, we aimed to determine the mechanisms that G. tenuifolia assist TRAIL-induced apoptosis of hepatoma cell. We found that administration of G. tenuifolia ethyl acetae extract (GT/EA) increased TRAIL-induced apoptosis in hepatoma cell line (Hep 3B). With western blotting, GT/EA could enhance poly (ADP-ribose) polymerase-1 (PARP-1) cleavage in the TRAIL-induced cell death pathway. Cellular FLICE (FADD-like　IL-1β-converting enzyme)-inhibitory protein (c-FLIP) is a major anti-apoptotic protein in death receptor, including TRAIL, induced apoptosis. Further examination demonstrated that c-FLIP was downregulated in GT/EA-treated Hep 3B cells. This study concludes that G. tenuifolia could increase TRAIL-induced apoptosis in hepatoma involving down regulation of c-FLIP.