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題 名 | Down-regulation of Fatty Acid Synthase is Associated with Decreased Akt Activation in Lovastatin Induced Apoptosis Cells=Lovaststin在誘發凋亡細胞中表現降低的脂肪酸合成酶與AKT活化作用 |
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作 者 | 張源清; 黃彥華; 施純明; 吳瑞裕; 劉建良; 王淑慧; 林俊茂; | 書刊名 | 藥物食品分析 |
卷 期 | 14:4 民95.12 |
頁 次 | 頁340-345+405 |
分類號 | 418.31 |
關鍵詞 | 脂肪酸合成酶; 洛婓史達汀; 史達汀; AKT; PKB; PPAR; SREBP; Fatty acid synthase; Lovastatin; Statin; |
語 文 | 英文(English) |
中文摘要 | 脂肪酸合成酶之蛋白質表現的增加與癌症之發展呈現正相關關係,因此脂肪酸合成酶抑制作用提供了發展抗癌藥物的新目標。Lovastatin是紅麴菌Monascus purourous發酵產物的活性成分。在許多的癌細胞中,Lovastatin可抑制細胞分裂並誘發細胞凋亡。本報告揭露Lovastatin透過抑制脂肪酸合成酶的作用達到癌症化學預防的功效。以Lovastatin處理HL-60細胞,可誘發細胞凋亡。以流式細胞儀偵測次G1峰值為49.83%相對於控制組為10.43%,且可觀察到皰狀細胞膜形態及細胞核緊縮。以50 μM Lovastatin處理HepG2細胞4小時,細胞三酸甘油酯、膽固醇及脂肪酸含量分別下降到控制組中含量的79%、81%及75%。若分別以0、10、20及50 μM Lovastatin處理細胞,脂肪酸合成酶的相對蛋白質量分別為1.00、0.89、0.72及0.31。其Akt磷酸化程度顯現濃度依賴方式的下降。以反轉錄聚合酶鏈反應技術,分析Lovastatin處理過的HepG2細胞之RNA表現,顯示Lovastatin可活化Peroxisome Proliferator-Activated Receptor-gamma的RNA表現,並且抑制Sterol-regulatory element binding protein-1的RNA表現。此一結果首度揭露了Lovastatin降低脂肪酸合成酶的表現功效與脂肪酸合成酶上游調節者-Akt磷酸化活化的抑制作用具有關聯性。 |
英文摘要 | Increased fatty acid synthase (FAS) protein expression is coordinated with cancer development. FAS inhibitors become a focus of anticancer drug development. Lovastatin, one of the active ingredients in red yeast rice, is a product of Monascus purpureus. Lovastatin has been shown to inhibit proliferation and to induce apoptosis in a variety of tumor cells. This report shows that chemopreventive effects of lovastatin may be through the down regulation of FAS. Lovastatin exhibited significant apoptosis-inducing activity in HL-60 cells, as observed by flow cytometry (with 49.83% in sub-G1 peak compared to the control, 10.43%), blebbing cell membrane morphology, and nuclear condensation. Cellular triglyceride, cholesterol, and free fatty acid in HepG2 cells were reduced to 79%, 81%, and 75%, respectively, upon lovastatin treatment (50 μM) for 4 h. The relative levels of FAS protein after treatment with 0, 10, 20, and 50 μM lovastatin were 1.00, 0.89, 0.72, and 0.31, respectively. Phosphorylated Akt was reduced in a dose-dependent manner. Reverse transcription PCR analysis showed that lovastatin upregulated PPAR-γ and inhibited SREBP-1 mRNA expression in HepG2 cells. Our current results implicate that lovastatin inhibiting FAS expression is associated with the decreased Akt activation. |
本系統中英文摘要資訊取自各篇刊載內容。