Research Paper Volume 13, Issue 9 pp 12514—12525
Capsanthin induces G1/S phase arrest, erlotinib-sensitivity and inhibits tumor progression by suppressing EZH2-mediated epigenetically silencing of p21 in triple-negative breast cancer cells
- 1 Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan
- 2 Ph.D. Program for Translational Medicine, China Medical University, Taichung 40402, Taiwan
- 3 Institute of New Drug Development, China Medical University, Taichung 40402, Taiwan
- 4 Drug Development Center, Research Center for Cancer Biology, China Medical University, Taichung 40402, Taiwan
- 5 Center for Molecular Medicine, China Medical University Hospital, Taichung 40402, Taiwan
- 6 Division of Breast Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan
- 7 Department of Applied Cosmetology, College of Human Science and Social Innovation, Hungkuang University, Taichung 43302, Taiwan
- 8 School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan
- 9 Department of Surgery, China Medical University Hospital, Taichung 40402, Taiwan
- 10 Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung 41354, Taiwan
Received: November 17, 2020 Accepted: March 5, 2021 Published: May 2, 2021
https://doi.org/10.18632/aging.202925How to Cite
Abstract
Capsanthin is a naturally occurring red pepper carotenoid with possible antitumor activity, but its antitumor mechanisms have yet to be delineated. We tested the anti-proliferative activity of capsanthin with human triple-negative breast cancer (TNBC) and found that cell proliferation was inhibited after 24, 48 and 72 h of treatment. We also investigated the cellular and molecular mechanisms of the antitumor efficacy of capsanthin on TNBC cells and found that capsanthin delayed cell-cycle progression at the G1/S stage, that cyclin A expression was suppressed, and that p21 expression was upregulated. Capsanthin also inhibited the EZH2 expression and EZH2 could binding to the p21 promoter in TNBC cells. We further discovered that capsanthin has synthetic effects when combined with erlotinib (Tarceva). In the animal experiment, we found that the capsanthin-induced inhibition of TNBC cell proliferation decreased the incidence of the initiation and growth of TNBC cell–derived tumors in mice. Our study reveals that capsanthin exerted antitumor effects through delaying cell-cycle progression, induces erlotinib-sensitivity and inhibits tumor progression by inhibiting EZH2/p21 axis, and capsanthin is a potential drug candidate for development of a safe and effective therapy against TNBCs, especially for TNBCs that have developed resistance to targeting therapy.