Studies on the molecular mechanisms of Menadione-induced G0/G1 cell-cycle arrest in MDA-MB 231 Human Breast Cancer cells

• Main Authors: Wen-Chien Hsu, 許文建
• Other Authors: 何元順
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/96314148827277511177

碩士 === 臺北醫學大學 === 醫學檢驗生物技術學研究所 === 95 === 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 .