8-Chrysoeriol, as a potential BCL-2 inhibitor triggers apoptosis of SW1990 pancreatic cancer cells

Yiwen Zhang; Zhimei Li; Qiuxia Min; Abulizi Palida; Yiyuan Zhang; Ruotian Tang; Lixia Chen; Hua Li

doi:10.1016/j.bioorg.2018.01.042

8-Chrysoeriol, as a potential BCL-2 inhibitor triggers apoptosis of SW1990 pancreatic cancer cells

Bioorg Chem. 2018 Apr:77:478-484. doi: 10.1016/j.bioorg.2018.01.042. Epub 2018 Feb 2.

Authors

Yiwen Zhang¹, Zhimei Li², Qiuxia Min², Abulizi Palida³, Yiyuan Zhang², Ruotian Tang⁴, Lixia Chen⁵, Hua Li⁶

Affiliations

¹ Wuya College of Innovation, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
² Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
³ Department of Pharmacy, Xinjiang Medical University, Urumpi, Xinjiang 830011, China.
⁴ Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: 676264176@qq.com.
⁵ Wuya College of Innovation, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: syzyclx@163.com.
⁶ Wuya College of Innovation, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China; Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: li_hua@hust.edu.cn.

PMID: 29454280
DOI: 10.1016/j.bioorg.2018.01.042

Abstract

8-Chrysoeriol, a bioactive flavanoid, was firstly identified to bind directly to BCL-2 as BH3 mimetics by structure-based virtual ligand screening. And 3D docking model revealed the molecular basis of 8-Chrysoeriol targeting to BCL-2. The interaction between 8-Chrysoeriol and BCL-2 was further confirmed using Microscale Thermophoresis (MST) technique. Meanwhile, high expression level of antiapoptotic protein BCL-2 was detected in SW1990 pancreatic cancer cells and 8-Chrysoeriol showed obvious proapoptosis effect against SW1990 in vitro. Collectively, the results showed that 8-Chrysoeriol as a natural dietary product potentially targeting to BCL-2 could serve as a lead compound for SW1990 pancreatic cancer therapy.

Keywords: BCL-2 inhibitor; BH3 mimetics; SW1990 pancreatic cancer.

Publication types

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

MeSH terms

Antineoplastic Agents, Phytogenic / chemistry
Antineoplastic Agents, Phytogenic / isolation & purification
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects*
Cell Survival / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Flavones / chemistry
Flavones / isolation & purification
Flavones / pharmacology*
Humans
Ligands
Molecular Docking Simulation
Molecular Structure
Pancreatic Neoplasms / drug therapy*
Pancreatic Neoplasms / metabolism
Pancreatic Neoplasms / pathology
Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
Proto-Oncogene Proteins c-bcl-2 / metabolism
Structure-Activity Relationship
Tumor Cells, Cultured

Substances

Antineoplastic Agents, Phytogenic
BCL2 protein, human
Flavones
Ligands
Proto-Oncogene Proteins c-bcl-2
chrysoeriol