Peptide SA12 inhibits proliferation of breast cancer cell lines MCF-7 and MDA-MB-231 through G0/G1 phase cell-cycle arrest

Abstract

Longfei Yang,1,* Huanran Liu,2,* Min Long,1 Xi Wang,1 Fang Lin,1 Zhaowei Gao,1 Huizhong Zhang1 1Department of Medical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi’an, China; 2Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, China *These authors contributed equally to this work Background: Targeted therapies have been proven as promising in the treatment of breast cancer and have improved survival and quality of life in advanced breast cancer. We previously identified a novel peptide SA12 which showed significant activity in the inhibition of proliferation and induction of apoptosis in SKBr-3 cells. Methods: The present study investigated the potential antitumor role of SA12 in breast cancer cell lines MDA-MB-231 and MCF-7 through Cell Counting Kit-8 assay and colony formation assay, and examined the cell cycle distribution using flow cytometry analysis. Furthermore, the expression of cell cycle-related genes cyclin D1, CDK4, and tumor suppressor gene p16 were examined by real-time polymerase chain reaction and Western blot to explore the molecular mechanism. Results: We determined that peptide SA12 suppressed the proliferation of MDA-MB-231 and MCF-7 cell lines through the G0/G1 phase cell cycle arrest. Moreover, the expressions of cell cycle-associated genes cyclin D1 and CDK4 were downregulated and the expression of tumor suppressor gene p16 was upregulated after treatment with SA12. MECP2 was required for the enhanced expression of p16 gene induced by SA12, which further inhibits CDK4/CDK6 activation and arrests the cell cycle progression from G0/G1 to S phase.Conclusion: We concluded that SA-12 inhibits the proliferation of MCF-7 and MDA-MB-231 cells through G0/G1 cell cycle arrest. Cell cycle related genes cyclin D1, CDK4, and p16 participate in the process, and MECP2 is essential for the enhanced expression of p16 gene induced by SA-12. Keywords: SA12, breast cancer, G0/G1 arrest, cyclin D1, CDK4, p16

Keywords

• Peptide SA12 inhibits proliferation of MCF-7 and MDA-MB-231 cells