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

• Published in: International journal of molecular sciences Vol. 20; no. 5; p. 1164
• Main Authors: Tang, Kai Dun, Liu, Ji, Russell, Pamela J, Clements, Judith A, Ling, Ming-Tat
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07.03.2019; MDPI
• Subjects: Angiogenesis; angiopoietin-1; Apoptosis; Autocrine signalling; Autophagy; Cell growth; Chemotherapy; Cytotoxicity; Epidermal growth factor; Epidermal growth factor receptors; Epithelial cells; Experiments; gamma-tocotrienol and autophagy; Growth factors; Hypotheses; Kinases; mRNA; NF-κB protein; Phosphorylation; Prostate cancer; Protein expression; Proteins; Radiation therapy; Secretion; Signal transduction; Tie-2; Tumor cell lines; angiopoietin-1; prostate cancer; gamma-tocotrienol and autophagy; Tie-2
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20051164

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.