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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Antioxidants, Blotting, Western, Breast Neoplasms, Cell Death, Cell Line, Tumor, Chromans, Colonic Neoplasms, Extracellular Signal-Regulated MAP Kinases, Female, Flow Cytometry, Humans, Microscopy, Fluorescence, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Real-Time Polymerase Chain Reaction, Signal Transduction, Spheroids, Cellular, Uterine Cervical Neoplasms, Vitamin E, ras Proteins.
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Does gamma tocotrienol target tyrosine phosphatase SHP2 in mammospheres resulting in cell death through RAS/ERK pathway? Context: There is increasing evidence supporting the concept of cancer stem cells (CSCs), which are responsible for the initiation, growth and metastasis of tumors. CSCs are thus considered the target for future cancer therapies. To achieve this goal, identifying potential therapeutic targets for CSCs is essential. We used a natural product of vitamin E, gamma tocotrienol (gamma-T3), to treat mammospheres and spheres from colon and cervical cancers. Western blotting and real-time RT-PCR were employed to identify the gene and protein targets of gamma-T3 in mammospheres. We found that mammosphere growth was inhibited in a dose dependent manner, with total inhibition at high doses. Gamma-T3 also inhibited sphere growth in two other human epithelial cancers, colon and cervix. Our results suggested that both Src homology 2 domain-containing phosphatase 1 (SHP1) and 2 (SHP2) were affected by gamma-T3 which was accompanied by a decrease in K- and H-Ras gene expression and phosphorylated ERK protein levels in a dose dependent way. In contrast, expression of self-renewal genes TGF-beta and LIF, as well as ESR signal pathways were not affected by the treatment. These results suggest that gamma-T3 specifically targets SHP2 and the RAS/ERK signaling pathway.
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SHP1 and SHP2 are potential therapeutic targets for breast CSCs and gamma-T3 is a promising natural drug for future breast cancer therapy. Final Decision: yes