人類肝癌在全球好發癌症中排名第五位，並在癌症致死率中排名上升至第三位，然而目前對於肝癌的治療及預後效果仍不盡人意。過去原住民普遍有利用煎煮福木果實來做藥的偏方來針對疑難雜症進行治療，近年來的文獻也記載福木的果實及樹皮萃取物中具有抑制DNA topoisomerase、抗發炎及對腫瘤細胞具毒殺特性的物質存在。本篇論文所使用的GP-1是由福木的果皮中萃取出的單一天然物質，在處理人類肝癌Hep-3B細胞後能抑制其生長，六天後其抑制Hep-3B細胞50％細胞生長濃度(IC50)為12.84M。以GP-1處理Hep-3B細胞之後發現細胞sub-G1期DNA比例的增加、DNA有片段化等細胞凋亡時的現象出現，因而得知GP-1可透過引發凋亡的機制而抑制Hep-3B細胞生長；以西方墨點法分析GP-1誘導Hep-3B細胞凋亡的途徑，發現有caspase-2及caspase-8的活化，細胞質中Bid的表現量減少，另以DiOC6(3)進行染色，發現粒線體膜電位的喪失，cytochrome c以及Smac/DIABLO自粒線體釋放至細胞質中，活化caspase-9及caspase-3並抑制XIAP表現，而細胞核內AIF以及DFF40的表現都有增加的趨勢。本實驗發現GP-1能引起粒線體膜電位的改變並透過caspase cascade造成Hep-3B細胞的細胞凋亡，本研究結果描繪出GP-1誘導Hep-3B細胞凋亡的訊息傳遞路徑，期望在將來可供抗癌藥物研發及臨床用藥之參考。

Human hepatocellular carcinoma (HCC) is the fifth most frequent cancer and is the third most common cause of cancer-related death worldwide. Unfortunately, it does not response well to chemotherapy and has a poor prognosis of patients. The crude extract of the pericarp of Garcinia subelliptica (G. subelliptica) is a remedy commonly using to treat patients of aborigine in Taiwan. Previous studies have reported that constituents of the wood and root bark of G. subelliptica containing some compounds possess inhibitory activity against DNA topoisomerase, and the anti-inflammatory activity. Recent study has shown that a new benzoylphloroglucinol, garcinielliptone FB extracted from the pericarp of G. subelliptica exhibits cytotoxic activity against several tumor cells. The present study demonstrates that GP-1, a novel pure compound isolated from G. subelliptica, inhibited growth of HCC Hep-3B cells with the IC50 of 12.84 M at day 6 of post-treatment. This inhibitory effect may be due to the process of apoptosis which was characterized by increase of sub-G1 DNA content and production of DNA fragments. The mechanism of apoptosis may be associated with the activation of caspase-2 and caspase-8, decrease cytosolic Bid, loss of mitochondrial membrane potential, release of cytochrome c and Smac/DIABLO to cytosol, decrease of XIAP, induction of caspase-9 and caspase-3, and elevation of nuclear DFF40. Moreover, AIF was released from mitochondria and entered to the nucleus in response to GP-1. These findings described the signaling pathway in GP-1 treated Hep-3B cells, and may provide a new sight of anti-cancer drug for clinical use.

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