期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 20, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/ijms20051164
关键词
prostate cancer; angiopoietin-1; Tie-2; gamma-tocotrienol and autophagy
资金
- QUT-MACC HDR Tuition Award
- QUT Supervisor Scholarship
- National Health and Medical Research Council (NHMRC) [APP1031221, APP1031228]
- NHMRC Principal Research Fellowship
- Australian Government Department of Health
- Australian Government
Emerging evidence suggests that gamma-tocotrienol (-T3), a vitamin E isomer, has potent anti-cancer properties against a wide-range of cancers. -T3 not only inhibited the growth and survival of cancer cells in vitro, but also suppressed angiogenesis and tumour metastasis under in vivo conditions. Recently, -T3 was found to target cancer stem cells (CSCs), leading to suppression of tumour formation and chemosensitisation. Despite its promising anti-cancer potential, the exact mechanisms responsible for the effects of -T3 are still largely unknown. Here, we report the identification of Ang-1 (Angiopoietin-1)/Tie-2 as a novel -T3 downstream target. In prostate cancer cells, -T3 treatment leads to the suppression of Ang-1 at both the mRNA transcript and protein levels. Supplementing the cells with Ang-1 was found to protect them against the anti-CSC effect of -T3. Intriguingly, inactivation of Tie-2, a member receptor that mediates the effect of Ang-1, was found to significantly enhance the cytotoxic effect of -T3 through activation of AMP-activated protein kinase (AMPK) and subsequent interruption of autophagy. Our results highlighted the therapeutic potential of using -T3 in combination with a Tie-2 inhibitor to treat advanced prostate cancer.
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