Open AccessCapsanthin 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
Author(s) -
Jiayan Wu,
Yi-Chung Chien,
I-Chen Tsai,
ChihChiang Hung,
WeiChien Huang,
LiangChih Liu,
YungLuen Yu
Publication year - 2021
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.202925
Subject(s) - cancer research , triple negative breast cancer , erlotinib , cell growth , gene silencing , cell cycle , biology , cell cycle checkpoint , ezh2 , tumor progression , chemistry , cell , cancer , breast cancer , gene expression , epidermal growth factor receptor , biochemistry , gene , genetics
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.