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Article

Gamma-Tocotrienol Induces Apoptosis in Prostate Cancer Cells by Targeting the Ang-1/Tie-2 Signalling Pathway

The School of Biomedical Sciences, Australian Prostate Cancer Research Centre-Queensland & Institute of Health and Biomedical Innovation, Queensland University of Technology and The Translational Research Institute, Queensland 4102, Australia
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Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(5), 1164; https://doi.org/10.3390/ijms20051164
Received: 29 January 2019 / Revised: 4 March 2019 / Accepted: 5 March 2019 / Published: 7 March 2019
Emerging evidence suggests that gamma-tocotrienol (γ-T3), a vitamin E isomer, has potent anti-cancer properties against a wide-range of cancers. γ-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, γ-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 γ-T3 are still largely unknown. Here, we report the identification of Ang-1 (Angiopoietin-1)/Tie-2 as a novel γ-T3 downstream target. In prostate cancer cells, γ-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 γ-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 γ-T3 through activation of AMP-activated protein kinase (AMPK) and subsequent interruption of autophagy. Our results highlighted the therapeutic potential of using γ-T3 in combination with a Tie-2 inhibitor to treat advanced prostate cancer. View Full-Text
Keywords: prostate cancer; angiopoietin-1; Tie-2; gamma-tocotrienol and autophagy prostate cancer; angiopoietin-1; Tie-2; gamma-tocotrienol and autophagy
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MDPI and ACS Style

Tang, K.D.; Liu, J.; Russell, P.J.; Clements, J.A.; Ling, M.-T. Gamma-Tocotrienol Induces Apoptosis in Prostate Cancer Cells by Targeting the Ang-1/Tie-2 Signalling Pathway. Int. J. Mol. Sci. 2019, 20, 1164. https://doi.org/10.3390/ijms20051164

AMA Style

Tang KD, Liu J, Russell PJ, Clements JA, Ling M-T. Gamma-Tocotrienol Induces Apoptosis in Prostate Cancer Cells by Targeting the Ang-1/Tie-2 Signalling Pathway. International Journal of Molecular Sciences. 2019; 20(5):1164. https://doi.org/10.3390/ijms20051164

Chicago/Turabian Style

Tang, Kai D., Ji Liu, Pamela J. Russell, Judith A. Clements, and Ming-Tat Ling. 2019. "Gamma-Tocotrienol Induces Apoptosis in Prostate Cancer Cells by Targeting the Ang-1/Tie-2 Signalling Pathway" International Journal of Molecular Sciences 20, no. 5: 1164. https://doi.org/10.3390/ijms20051164

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