Identification of a Novel Bcl-2 Inhibitor by Ligand-Based Screening and Investigation of Its Anti-cancer Effect on Human Breast Cancer Cells

Mei Wen, Zhen Ke Deng, Shi Long Jiang, Yi Di Guan, Hai Zhou Wu, Xin Luan Wang, Song Shu Xiao, Yi Zhang, Jin Ming Yang, Dong Sheng Cao, Yan Cheng

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Bcl-2 family protein is an important factor in regulating apoptosis and is associated with cancer. The anti-apoptotic proteins of Bcl-2 family, such as Bcl-2, are overexpression in numerous tumors, and contribute to cancer formation, development, and therapy resistance. Therefore, Bcl-2 is a promising target for drug development, and several Bcl-2 inhibitors are currently undergoing clinical trials. In this study, we carried out a QSAR-based virtual screening approach to develop potential Bcl-2 inhibitors from the SPECS database. Surface plasmon resonance (SPR) binding assay was performed to examine the interaction between Bcl-2 protein and the screened inhibitors. After that, we measured the anti-tumor activities of the 8 candidate compounds, and found that compound M1 has significant cytotoxic effect on breast cancer cells. We further proved that compound M1 downregulated Bcl-2 expression and activated apoptosis by inducing mitochondrial dysfunction. In conclusion, we identified a novel Bcl-2 inhibitor by QSAR screening, which exerted significant cytotoxic activity in breast cancer cells through inducing mitochondria-mediated apoptosis.

Original languageEnglish
Article number391
JournalFrontiers in Pharmacology
Volume10
Issue numberMAR
DOIs
StatePublished - 2019

Bibliographical note

Publisher Copyright:
© 2019 Wen, Deng, Jiang, Guan, Wu, Wang, Xiao, Zhang, Yang, Cao and Cheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Keywords

  • Bcl-2
  • Breast cancer cell
  • QSAR
  • Small molecule inhibitors
  • Virtual screening

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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