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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.
Wu, Jia-Yan; Chien, Yi-Chung; Tsai, I-Chen; Hung, Chih-Chiang; Huang, Wei-Chien; Liu, Liang-Chih; Yu, Yung-Luen.
Afiliación
  • Wu JY; Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan.
  • Chien YC; Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan.
  • Tsai IC; Ph.D. Program for Translational Medicine, China Medical University, Taichung 40402, Taiwan.
  • Hung CC; Institute of New Drug Development, China Medical University, Taichung 40402, Taiwan.
  • Huang WC; Drug Development Center, Research Center for Cancer Biology, China Medical University, Taichung 40402, Taiwan.
  • Liu LC; Center for Molecular Medicine, China Medical University Hospital, Taichung 40402, Taiwan.
  • Yu YL; Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan.
Aging (Albany NY) ; 13(9): 12514-12525, 2021 05 02.
Article en En | MEDLINE | ID: mdl-33934088
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Proliferación Celular / Neoplasias de la Mama Triple Negativas Tipo de estudio: Diagnostic_studies Límite: Animals / Humans Idioma: En Revista: Aging (Albany NY) Asunto de la revista: GERIATRIA Año: 2021 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Proliferación Celular / Neoplasias de la Mama Triple Negativas Tipo de estudio: Diagnostic_studies Límite: Animals / Humans Idioma: En Revista: Aging (Albany NY) Asunto de la revista: GERIATRIA Año: 2021 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos