A new study with the participation of Mind the Byte has identified a new group of phytochemicals capable of specifically and potently suppressing the functional traits of Cancer Stem Cells (CSC). The research was led by the group of Metabolism and Cancer of the Catalan Institute of Oncology (ICO) – Girona Biomedical Research Institute (IDIBGI) and has been published in the scientific journal Carcinogenesis.
Targeting tumor-initiating, drug-resistant populations of CSC with phytochemicals is a novel paradigm for cancer prevention and treatment. The team of scientists have employed a phenotypic drug discovery approach coupled to mechanism-of-action profiling and target deconvolution to identify phenolic components of extra virgin olive oil capable of suppressing the functional traits of CSC in breast cancer.
In vitro screening revealed that the polyphenol DOA could selectively target certain subpopulations of CSC. Therefore, DOA could potently block the formation of multicellular tumorspheres generated from single-founder stem-like cells in a panel of genetically diverse breast cancer models.
Pretreatment of breast cancer populations with DOA dramatically reduced subsequent tumor-forming capacity in vivo. In that regard, mice injected with CSC-enriched BC-cell populations pretreated with DOA remained tumor-free for several months.
In silico computational studies by Mind the Byte indicated that DOA binds and inhibits the ATP-binding kinase domain site of mTOR and the S-adenosyl-l-methionine (SAM) cofactor-binding pocket of DNA methyltransferases. FRET-based Z-LYTE™ and AlphaScreen-based in vitro assays confirmed the computationally predicted ability of DOA to function as an ATP-competitive mTOR inhibitor and to block the SAM-dependent methylation activity of DNMTs.
Reference Article: Corominas-Faja B, Cuyàs E, Lozano-Sánchez J, Cufí S, Verdura S, Fernández-Arroyo S, Borrás-Linares I, Martin-Castillo B, Martin ÁG, Lupu R, Nonell-Canals A, Sanchez-Martinez M, Micol V, Joven J, Segura-Carretero A, Menendez JA. Extra-virgin olive oil contains a metabolo-epigenetic inhibitor of cancer stem cells. Carcinogenesis. 2018 Feb 14. doi: 10.1093/carcin/bgy023.