Anticancer activity of britannin through the downregulation of cyclin D1 and CDK4 in human breast cancer cells

Abstract

Aim of the Study: Both apoptotic induction and cell cycle blockade in cancer cells are effective strategies to eliminate cancer cells. Many conventional cancer drugs that induce apoptosis and inhibit cell cycle progression have been reported as potential therapeutics for various types of cancer. Britannin is a natural sesquiterpene lactone that its profound anticancer properties were revealed in our previous study. In this study, we evaluated the effects of britannin on the cell cycle distribution and also cell cycle-related proteins. Materials and Methods: Analysis of cell cycle distribution was carried out using flow cytometer. The effects of britannin on cyclin D1 and CDK4 expression were evaluated using the Western blot. Results: The obtained results show that britannin at the low concentrations induces cell growth inhibition mainly through G1-phase arrest while it seems that apoptosis contributes to cell growth inhibitory effect of high doses of britannin. Reduction of cyclin D1 and CDK4 protein levels were also observed after treating cancer cells with britannin. Conclusion: The obtained results reveal that britannin can inhibit MCF-7 and MDA-MB-468 breast cancer cells proliferation through arresting cell cycle progression through cyclin D1/CDK4-mediated pathway.