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• W1878166905 endingPage "435" @default.
• W1878166905 startingPage "421" @default.
• W1878166905 abstract "Aberrant c-Myc activity plays a central role in cancer transformation. γ-tocotrienol is a member of the vitamin E family that displays potent anti-cancer activity. Here, studies were conducted to determine the role of c-Myc in mediating anti-proliferative effects of γ-tocotrienol in mammary cancer cells.Treatment effects on mouse +SA and human MCF-7 mammary cancer cell proliferation were determined by MTT assay and Ki-67 staining. Protein expression was determined by western blot analysis. Immunofluorescence staining and qRT-PCR were used to characterize cellular c-Myc and MYC levels respectively.Anti-proliferative effects of γ-tocotrienol were associated with reduction in total c-Myc and phosphorylated-c-Myc-serine 62, and increase in phosphorylated-c-Myc-threonine 58 levels. γ-tocotrienol also reduced PI3K/Akt/mTOR and Ras/MEK/Erk mitogenic signalling, cyclin D1 and cyclin-dependent kinase 4 levels, and increased p27 levels. However, γ-tocotrienol had no effect on MYC mRNA levels. γ-tocotrienol also increased levels of FBW7 (E3 ligase that initiates ubiquitination of c-Myc), but had no effect on serine/threonine phosphatase PP2A or isomerase Pin 1 levels. Combined treatment with GSK3α/β inhibitor LiCl or proteasome inhibitor MG132 blocked γ-tocotrienol-induced reductions in c-Myc.These findings indicate that anti-proliferative effects of γ-tocotrienol are associated with reduction in c-Myc that results from increase in GSK-3α/β-dependent ubiquitination and degradation, rather than from reduction in c-Myc synthesis in +SA and MCF-7 mammary cancer cells." @default.
• W1878166905 created "2016-06-24" @default.
• W1878166905 creator A5059085312 @default.
• W1878166905 creator A5061101570 @default.
• W1878166905 creator A5085552336 @default.
• W1878166905 date "2015-06-19" @default.
• W1878166905 modified "2023-10-05" @default.
• W1878166905 title "Anti-proliferative effects of γ-tocotrienol are associated with suppression of c-Myc expression in mammary tumour cells" @default.
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• W1878166905 doi "https://doi.org/10.1111/cpr.12196" @default.
• W1878166905 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6496305" @default.
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• W1878166905 hasPublicationYear "2015" @default.
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