Induction of G1 cell cycle arrest and cyclin D1 down-regulation in response to pericarp extract of Baneh in human breast cancer T47D cells

In order to study the possible effect of Baneh extract on cell cycle of T47D cells, we evaluated cell cycle distribution and its regulatory proteins by flow cytometry and western blot analysis respectively.Baneh extract induced G0/G1 cell cycle arrest in conjunction with a marked decrease in expression of cyclin D1 and cdk4 that was strongly dependent on time of exposure. In parallel, Dox-treated T47D cells in early time points were accumulated on S phase, but after 48 h cell cycle progression was inhibited on G2/M. Dox promoted striking accumulation of cyclin B1 rapidly and enhanced cyclin A abundance.Taken together, our results establish that the antitumor activity of the pericarp extract of Baneh partly is mediated via cell cycle arrest and downregulation of cyclin D1 and cdk4 expression. These findings warrant further evaluation regarding the mechanism(s) of action of this promising anticancer agent.Breast cancer is one of the most common cancers in women worldwide and Iran in particular. Each year over 1.15 million women are diagnosed with breast cancer and nearly half of them die [1]. Thus, new therapeutic steps should be taken both to prevent the development of cancer and to lower mortality rates related to it.The characteristic feature of tumor cells is uncontrolled cell growth as a result of alterations in a variety of molecules and regulatory pathways involved in cell cycle control [2]. Mitogenic signals induce cyclin D1 expression and binding to cdk4/ or cdk6 in G1 phase of the cell cycle. Then cyclin E/cdk2 activated in late G1 phase. Cdk2 forms complex with cyclin A in S phase to induce proteins which involved in DNA replication. Cdk1/cyclin A is necessary for initiation of prophase and finally cdk1/cyclin B complex takes part in and completes mitosis [3].Lately, a significant increase has been seen in the search for new effective cancer chemopreventive and chemotherapeutic agents, particularly for those that have a natural origin and relatively low tox