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
- 1 Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China
- 2 Department of Neurology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan,, China
- 3 Key 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
- 4 Kunming College of Life Science, University of the Chinese Academy of Sciences, Kunming 650204, China
- 5 Medical Faculty of Kunming University of Science and Technology, Kunming 650500, China
- 6 College of Chemistry, Fuzhou University, Fuzhou 350116, Fujian, China
- 7 Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao 266071, China
- 8 Translational Cancer Research Center, Peking University First Hospital, Beijing 100034, China
- 9 KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
- 10 Institute of Translation Medicine, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China
Received: November 21, 2019 Accepted: April 17, 2020 Published: May 23, 2020
https://doi.org/10.18632/aging.103232How to Cite
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.