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Curcumin suppresses LGR5(+) colorectal cancer stem cells by inducing autophagy and via repressing TFAP2A-mediated ECM pathway.
Mao, Xiaohong; Zhang, Xin; Zheng, Xiaowei; Chen, Yongwu; Xuan, Zixue; Huang, Ping.
Afiliación
  • Mao X; Department of Pharmacy, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, China.
  • Zhang X; Department of Pathology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, China.
  • Zheng X; Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou, 310022, China.
  • Chen Y; Department of Pharmacy, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230036, China.
  • Xuan Z; Department of Pharmacy, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, China. xuanzixue0222@163.com.
  • Huang P; Department of Pharmacy, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, China. huangping_zry@163.com.
J Nat Med ; 75(3): 590-601, 2021 Jun.
Article en En | MEDLINE | ID: mdl-33713277
Colorectal cancer stem cells (CSCs) have the potential for self-renewal, proliferation, and differentiation. And LGR5 is a stem cell marker gene of colorectal cancer. Curcumin can suppress oncogenicity of many cancer cells, yet the effect and mechanism of curcumin in LGR5(+) colorectal cancer stem cells (CSCs) have not been studied. In this study, we studied the effect of curcumin on LGR5(+) colorectal CSCs using the experiments of tumorsphere formation, cell viability and cell apoptosis. Then autophagy analysis, RNA-Seq, and real-time PCR were used to identify the mechanism responsible for the inhibition of LGR5(+) colorectal CSCs. Our results showed that curcumin inhibited tumorsphere formation, decreased cell viability in a dose-dependent manner, and also promoted apoptosis of LGR5(+) colorectal CSCs. Next, we found curcumin induced autophagy of LGR5(+) colorectal CSCs. When LGR5(+) colorectal CSCs were co-treated with curcumin and the autophagy inhibitor (hydroxychloroquine), curcumin-induced cell proliferation inhibition decreased. In addition, we also found that curcumin inhibited the extracellular matrix (ECM)-receptor interaction pathway via the downregulation of the following genes: GP1BB, COL9A3, COMP, AGRN, ITGB4, LAMA5, COL2A1, ITGB6, ITGA1, and TNC. Further, these genes were transcriptionally regulated by TFAP2A, and the high expression of TFAP2A was associated with poor prognosis in colorectal cancer. In conclusion, curcumin suppressed LGR5(+) colorectal CSCs, potentially by inducing autophagy and repressing the oncogenic TFAP2A-mediated ECM pathway.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Células Madre Neoplásicas / Neoplasias Colorrectales / Curcumina / Factor de Transcripción AP-2 Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Nat Med Asunto de la revista: TERAPIAS COMPLEMENTARES Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Japón
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Células Madre Neoplásicas / Neoplasias Colorrectales / Curcumina / Factor de Transcripción AP-2 Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Nat Med Asunto de la revista: TERAPIAS COMPLEMENTARES Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Japón