Luteolin inhibits cell proliferation and induces cell apoptosis via down-regulation of mitochondrial membrane potential in esophageal carcinoma cells EC1 and KYSE450

Abstract

// Ping Chen 1, 2 , Jing-Yang Zhang 1, 2 , Bei-Bei Sha 1, 2 , Yan-Er Ma 1, 2 , Tao Hu 1, 2 , Yang-Cheng Ma 1, 2 , Hao Sun 3 , Jian-Xiang Shi 3 , Zi-Ming Dong 1, 2 , Pei Li 1, 2 1 Cancer Chemoprevention Collaborative Innovation Center in Henan Province, Zhengzhou University, Zhengzhou, Henan, 450001, China 2 Department of Pathophysiology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China 3 College of Public Health, Henan Key Laboratory for Tumor Epidemiology, Affiliated Tumor Hospital, Zhengzhou University, Zhengzhou, Henan, 450001, China Correspondence to: Pei Li, email: lipeifreemai@zzu.edu.cn Zi-Ming Dong, email: Dongzm@zzu.edu.cn Jian-Xiang Shi, email: jianxiangshi@zzu.edu.cn Keywords: luteolin, esophageal squamous carcinoma, cell proliferation, mitochondrial membrane potential, chemotherapy Received: September 02, 2016     Accepted: February 06, 2017     Published: March 02, 2017 ABSTRACT In current study, we investigated the anti-tumor effect of luteolin in human ESCC cell lines in vitro and in vivo and tried to explore the potential mechanisms. Results from flow cytometry showed that luteolin could induce apoptosis and caspase-3 activation and induce cell cycle arrest at G2/M phase in a dose- and time-dependent manner in EC1 and KYSE450 cells. JC-1 test results showed that membrane potential of mitochondria after luteolin treatment was down-regulated and this was an indicator for intrinsic apoptosis. Western Blot results showed the expression of cell cycle regulatory protein p21 and p53 increased and three apoptosis related proteins that participate in mitochondrial apoptotic pathway, namely, Bim, CYT-c and cPARP, also increased in luteolin treated cells compared with control groups. We further confirmed that luteolin could significantly inhibit the growth of ESCC tumors in xenograft mouse models and no evidence of systemic toxicity was observed. Our results suggest that luteolin can induce cell apoptosis and cell cycle arrest in G2/M phase through mitochondrial pathway in EC1 and KYSE450 cell lines and proper utilization of luteolin might be a practical approach in ESCC chemotherapy.