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Farnesyl dimethyl chromanol targets colon cancer stem cells and prevents colorectal cancer metastasis.
Husain, Kazim; Coppola, Domenico; Yang, Chung S; Malafa, Mokenge P.
Afiliación
  • Husain K; Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Drive, Tampa, FL, 33612, USA.
  • Coppola D; Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
  • Yang CS; Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA.
  • Malafa MP; Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Drive, Tampa, FL, 33612, USA. mokenge.malafa@moffitt.org.
Sci Rep ; 11(1): 2185, 2021 01 26.
Article en En | MEDLINE | ID: mdl-33500430
The activation and growth of tumour-initiating cells with stem-like properties in distant organs characterize colorectal cancer (CRC) growth and metastasis. Thus, inhibition of colon cancer stem cell (CCSC) growth holds promise for CRC growth and metastasis prevention. We and others have shown that farnesyl dimethyl chromanol (FDMC) inhibits cancer cell growth and induces apoptosis in vitro and in vivo. We provide the first demonstration that FDMC inhibits CCSC viability, survival, self-renewal (spheroid formation), pluripotent transcription factors (Nanog, Oct4, and Sox2) expression, organoids formation, and Wnt/ß-catenin signalling, as evidenced by comparisons with vehicle-treated controls. In addition, FDMC inhibits CCSC migration, invasion, inflammation (NF-kB), angiogenesis (vascular endothelial growth factor, VEGF), and metastasis (MMP9), which are critical tumour metastasis processes. Moreover, FDMC induced apoptosis (TUNEL, Annexin V, cleaved caspase 3, and cleaved PARP) in CCSCs and CCSC-derived spheroids and organoids. Finally, in an orthotopic (cecum-injected CCSCs) xenograft metastasis model, we show that FDMC significantly retards CCSC-derived tumour growth (Ki-67); inhibits inflammation (NF-kB), angiogenesis (VEGF and CD31), and ß-catenin signalling; and induces apoptosis (cleaved PARP) in tumour tissues and inhibits liver metastasis. In summary, our results demonstrate that FDMC inhibits the CCSC metastatic phenotype and thereby supports investigating its ability to prevent CRC metastases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Neoplásicas / Neoplasias Colorrectales / Cromanos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Rep Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Neoplásicas / Neoplasias Colorrectales / Cromanos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Rep Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido