Evodiamine induces apoptosis and promotes hepatocellular carcinoma cell death induced by vorinostat via downregulating HIF-1α under hypoxia

Yang-Ling Li; Ning-Yu Zhang; Xiu Hu; Jia-Ling Chen; Ming-Jun Rao; Lin-Wen Wu; Qing-Yu Li; Bo Zhang; Wei Yan; Chong Zhang

doi:10.1016/j.bbrc.2018.03.004

Evodiamine induces apoptosis and promotes hepatocellular carcinoma cell death induced by vorinostat via downregulating HIF-1α under hypoxia

Biochem Biophys Res Commun. 2018 Apr 6;498(3):481-486. doi: 10.1016/j.bbrc.2018.03.004. Epub 2018 Mar 2.

Authors

Yang-Ling Li¹, Ning-Yu Zhang², Xiu Hu³, Jia-Ling Chen², Ming-Jun Rao⁴, Lin-Wen Wu³, Qing-Yu Li¹, Bo Zhang⁵, Wei Yan⁶, Chong Zhang⁷

Affiliations

¹ Department of Clinical Pharmacology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, Zhejiang, 310006, China.
² School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang, 310015, China.
³ School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang, 310015, China; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
⁴ Institute of Pharmacology, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 311402, China.
⁵ Hangzhou Translational Medicine Research Center, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, Zhejiang, 310006, China.
⁶ Department of Clinical Pharmacology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, Zhejiang, 310006, China. Electronic address: yanwei_115@163.com.
⁷ School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang, 310015, China. Electronic address: zhangchong@zucc.edu.cn.

PMID: 29505792
DOI: 10.1016/j.bbrc.2018.03.004

Abstract

Hypoxia promotes HCC progression and therapy resistance, and there is no systemic treatment for HCC patients after sorafenib resistance. Thus, it is urgent to develop potential therapeutic regimens for HCC patients by targeting hypoxia signaling. In this study, we showed that evodiamine might be a potential therapeutic medicine for HCC by suppressing HIF-1α. In addition, evodiamine could sensitize the anti-HCC effect of vorinostat in HCC cells under hypoxia. Furthermore, evodiamine plus vorinostat accelerated the degradation of HIF-1α in HCC cells under hypoxia. In general, evodiamine might be a potential therapeutic candidate for HCC patients, and evodiamine combining with vorinostat might be an attractive chemotherapy strategy for HCC treatment.

Keywords: Apoptosis; Combination; Evodiamine; HIF-1α; Hypoxia; Vorinostat.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / pharmacology*
Antineoplastic Agents, Phytogenic / pharmacology
Apoptosis / drug effects
Carcinoma, Hepatocellular / complications
Carcinoma, Hepatocellular / drug therapy*
Carcinoma, Hepatocellular / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects
Down-Regulation / drug effects
Drug Synergism
Humans
Hydroxamic Acids / pharmacology*
Hypoxia / complications
Hypoxia / drug therapy*
Hypoxia / metabolism
Hypoxia-Inducible Factor 1, alpha Subunit / analysis
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
Liver Neoplasms / complications
Liver Neoplasms / drug therapy*
Liver Neoplasms / metabolism
Quinazolines / pharmacology*
Vorinostat

Substances

Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Hydroxamic Acids
Hypoxia-Inducible Factor 1, alpha Subunit
Quinazolines
Vorinostat
evodiamine