Inhibition Of Cell Proliferation, Induction Of Apoptosis And Reactivation Of DLC1 By Flavone In Breast Cancer Cell Lines

Breast cancer was one of the most common female malignancies. The ages of breast cancer patients were yonger and yonger in our country, the overall peak age was 15 years earlier than western women. DLC1 has been shown to inhibit proliferation and induce apoptosis in a variety of human cancers, including breast cancer.Human breast cancer cells MCF7 were large and flat, with good refractivity in health conditions. They had short lifecycles, almost all cells can survive in this laboratory conditions. They were good materials research for breast cancer cells. So we used MCF cells as the research cells in the experiments.Flavonoids widely existed in plants as secondary metabolites. Soy isoflavones were found to exert physiological activities of cancer precaution, cardiovascular protection and prevention of osteoporosis and so on. In order to understand the molecular basis of the putative anticancer activity of flavonoids, we investigated whether and how the core structure of the flavones: flavone (2-phenyl-4H-1-benzopyran-4-one) affected proliferation, migration, the expression of DLC1 and apoptosis in MCF7 human breast cancer cell line. Proliferation was measured by MTT assay to ensure the most suitable concentration, we used flavone treated MCF7 cells for 48h, 72h and 96h, migration was measured by clonogenic assay, apoptosis and cell cycle distribution were measured by FACScan analysis. Semiquantitative reverse transcription PCR was performed to assess the effects of flavone on transcript levels of DLC1 and cell cycle related genes such as CyclinE and p21Waf1. Flavone was found to inhibit cell proliferation through MTT assays, in order to make the mechanism clear, we used FAScan assays to find the cell cycle distribution after the treatment of flavone, the cells wre found to arrest at G0/G1 and induce apoptosis in MCF7 cancer cell line. The flavonoid was proved to be a stronger apoptosis inducer. The effects of flavone in MCF7 cells were associated with changed mRNA levels of cell cycle and apoptosis related genes including Cyclin E and p21Waf1. Flavone was found to effectively inhibit migration and colonies through scratch assay and clongenic assay, semiquantitative RT-PCR was used to understand the mechanism, we found flavone up-regulated the expression of DLC1, inhibited the expression of ROCK mRNA, thereby further inhibited cell migration and colonies.These results indicated that flavone mediated alterations of genes which regulate cell cycle and apoptosis because of the antitumoral effects of flavone. Alone or in combination with anti-tumor agents, flavone may be an effective adjunct to chemotherapy in preventing breast cancer metastasis. Intaking the soy isoflavone can effectively reduce the risk of breast cancer in daily life.