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Research Paper|Volume 12, Issue 10|pp 9621—9632

Pyrrolo [3,4-b]-quinolin-9-amine compound FZU-0038-056 suppresses triple-negative breast cancer partially through inhibiting the expression of Bcl-2

Danping Wang1, Zhi Nie2,3,4, Xiaoyan Jiang5, Jinxiang Ye6, Zhimin Wei7, Dating Cheng1, Chenyang Wang1, Yingying Wu1,3,4, Rong Liu3,8, Haijun Chen6, Ceshi Chen3,9,10, Chunyan Wang1
  • 1Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China
  • 2Department of Neurology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan,, China
  • 3Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
  • 4Kunming College of Life Science, University of the Chinese Academy of Sciences, Kunming 650204, China
  • 5Medical Faculty of Kunming University of Science and Technology, Kunming 650500, China
  • 6College of Chemistry, Fuzhou University, Fuzhou 350116, Fujian, China
  • 7Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao 266071, China
  • 8Translational Cancer Research Center, Peking University First Hospital, Beijing 100034, China
  • 9KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
  • 10Institute of Translation Medicine, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China
* Equal contribution
Received: November 21, 2019Accepted: April 17, 2020Published: May 23, 2020

Copyright © 2020 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Triple-negative breast cancer (TNBC) has a poorer prognosis than other subtypes of breast cancer; however, it lacks effective targeted therapies clinically. In this study, we found FZU-0038-056, a novel compound derived from last-stage functionalization of tetrahydro-β-carboline scaffold, showed the most potent anti-cancer activity against TNBC cells among the 42 synthesized derivatives. We found FZU-0038-056 significantly induces apoptosis in HCC1806 and HCC1937 TNBC cells. FZU-0038-056 reduces the expression levels of several anti-apoptosis proteins, including Bcl-2, Mcl-1 and XIAP. Furthermore, we found FZU-0038-056 induces apoptosis partially through inhibiting the expression of Bcl-2. Finally, we found FZU-0038-056 significantly suppresses HCC1806 xenograft tumor growth in nude mice without affecting their body weight. Therefore, FZU-0038-056 has the potential to be a new anticancer agent for treating human TNBC.