Peptide SA12 inhibits proliferation of breast cancer cell lines MCF-7 and MDA-MB-231 through G0/G1 phase cell-cycle arrest
Authors Yang LF, Liu HR, Long M, Wang X, Lin F, Gao ZW, Zhang HZ
Received 30 October 2017
Accepted for publication 17 January 2018
Published 30 April 2018 Volume 2018:11 Pages 2409—2417
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 3
Editor who approved publication: Dr Samir Farghaly
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
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]