Menadione誘發人類乳癌細胞MDA-MB 231細胞週期G0/G1停滯之分子機制研究

Vitamin K是脂溶性維生素，以結構的不同分成K1(phylloquinone)、K2(menaquinones)、K3 (menadione)，其中K1來自日常飲食中的綠葉蔬菜，K2來自腸道中之細菌合成，而K3則是合成維生素，維生素主要功能為催化肝臟合成凝血因子prothrombin促進凝血機制。由過去文獻報告指出，Vitamin K也具有抗癌的效果，但作用機制不是完全清楚，目前了解依作用機制分成2種模式，一則是氧化模式(oxidative model)，透過氧化還原的方式大量產生過氧化物(ROS)，增加細胞氧化的負擔而進一步造成細胞死亡，另一則是非氧化模式( non oxidative model)由從轉錄因子來探討，Vitamin K會促進特定的轉錄因子表現進而調控細胞週期停滯及細胞凋亡。實驗中利用低濃度(5.8μM ) menadione對人類乳腺上皮細胞癌是否具有抗癌的效果以及分子作用機制討論。MTT及生長曲線的實驗，發現menadione在低濃度且長時間作用情況下，對在於人類乳腺上皮細胞癌(MDA-MB 231)是有明顯的抑制作用，而在正常乳腺細胞(MCF-10A)則沒有影響，在分子轉錄上及蛋白質表現方面也發現低濃度menadione處理24時能使MDA-MB 231誘發p21基因及蛋白表現量增加及cyclin E、CDK2抑制，再經由流式細胞儀分析也發現低濃度 menadione 處理24小時能使MDA-MB 231細胞週期GO/G1比例上升，造成細胞週期停滯，進而抑制細胞生長。而在調控p21基因表現的調節者部分，雖然沒有進一步發現，但也讓我們在未來可以朝此方向將menadione誘發p21基因表現的途徑呈現更完整。

關鍵字

維生素K3,人類乳癌細胞

並列摘要

Vitamin K is a family of structurally similar fat-soluble 2-methyl—1,4-naphtho-quinones,including phylloquinone(K1), menaquinones(K2),and menadione(K3). K1 is found in many green leafy vegetables. K2 is produced by a vast array of intestinal bacteria in human body. Menadione (K3) is not considered a natural vitamin K ,but rather a synthetic analoque acts as a provitamin .Vitamin K acts as a cofactor in normal blood coagulation from the post translation modification of a number of plasma proteins such as prothrombin. Vitamin K has been the focus of considerable research demonstrating an anticancer potential.However, yet the mechanisms of action remain unclear. A number mechanisms has been proposed and focused on the oxidative model which increased redox-cycling of menadione and the production of ROS surpasses the oxidative capacity of the cell, resulting in cell death. On the other hand, the non- oxidative model focuses on the modulation of transcriptionl factors which in turn induce cell cycle arrest and apoptosis. In our study, we found menadione has anticancer potential on human breast adenocarcinoma MDA MB 231 by weather cell cycle arrest, anti proliferation, or apoptosis. Low concentration of menadione (5.8μM) significant inhibited growth curve on breast cancer cells (MDA MB 231) but not breast cells (MCF 10A) by performing MTT and trypan blue cell counting. RT-PCR and western blotting showed menadione increase p21 gene and protein expressions but decrease cyclin E and CDK2 protein expression resulting in cell cycle G0/G1 arrest by flow cytometry. In the future, next step will be find out the key molecular proteins that regulate p21 expression and complete the whole view of mechanism by low concentration of menadione .

並列關鍵字

Menadione, MDA-MB 231

參考文獻

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Menadione誘發人類乳癌細胞MDA-MB 231細胞週期G0/G1停滯之分子機制研究

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