川陈皮素Nobiletin-食品科学系-国立屏东科技大学.DOCVIP

國立屏東科技大學食品科學系碩士班 　　　 　　　 研究生專題報告書面摘要 題目： 指導教授：陳和賢 博士 橘皮素和川陳皮素誘導人類乳癌及結腸癌細胞G1細胞週期停滯但非細胞凋亡 報 告 者：王俊堯 Tangeretin and nobiletin induce G1 cell cycle arrest but not apoptosis in human breast and colon cancer cells 報告日期：2010/05/26 摘要 柑橘類黃酮中橘皮素和川陳皮素在體外和體內試驗可以有效的抑制癌細胞生長。使用橘皮素和川陳皮素對人類乳腺癌細胞株MDA-MB- 435、MCF - 7和人類結腸癌細胞株HT - 29進行抗增殖活性的研究。結果顯示此兩種黃酮類化合物能抑制細胞增生，呈現劑量和時間依賴性，並使這三種細胞株的細胞週期停在G1。濃度結果顯示黃酮類化合物可以抑制癌細胞增生和細胞週期停滯但不會誘導細胞凋亡或細胞死亡。加入橘皮素和川陳皮素與細胞培養四天後，再與無加入黃酮類化合物培養4天的細胞比較，測試橘皮素和川陳皮素防止細胞恢復的能力。去除黃酮類及未處理控制組在培養一天內細胞恢復增生相似。而去除黃酮類及控制組在培養四天的細胞週期分佈相似。這些數據顯示，橘皮素和川陳皮素可以顯著抑制細胞增生是藉由細胞週期停滯而不是細胞凋亡，這些細胞株培養4天後，可以抑制細胞增生高達80％。橘皮素和川陳皮素不具細胞毒性可以有效的保護正常組織。因此，橘皮素和川陳皮素可以成為有效抑制細胞生長的抗癌藥物。抑制人類癌細胞增生而無誘導細胞死亡可能有利於治療腫瘤，這種限制癌細胞擴散的方式不太可能促使正常的細胞和非腫瘤組織產生細胞毒性和死亡。 關鍵字：橘皮素、川陳皮素、抗細胞增生、抑制細胞、乳癌、結腸癌 Abstrac Tangeretin and nobiletin are citrus flavonoids that are among the most effective at inhibiting cancer cell growth in vitro and in vivo. The antiproliferative activity of tangeretin and nobiletin was investigated in human breast cancer cell lines MDA-MB-435 and MCF-7 and human colon cancer line HT-29. Both flavonoids inhibited proliferation in a dose- and time-dependent manner, and blocked cell cycle progression at G1 in all three cell lines. At concentrations that resulted in significant inhibition of proliferation and cell cycle arrest, neither flavonoid induced apoptosis or cell death in any of the tumor cell lines. To test the ability of arrested cells to recover, cells that were incubated with tangeretin and nobiletin for 4 days were then cultured in flavonoid-free medium for an additional 4 days. Cells resumed proliferation similar to untreated control within a day of flavonoid removal. Cell cycle distribution was similar to that of control within 4 days of flavonoid removal. These data indicate that, in these cell lines at concentrations that inhibit proliferation up to 80% over 4 days, tangeretin and nobiletin are cytostatic and significantly suppress proliferation by cell cycle arrest without a