**7.6 Tocotrienols in prostate cancer**

Studies performed on human prostate carcinoma cells had shown that gammatocotrienol stimulated the process of apoptosis and autophagy in these cells. Gamma-tocotrienol supplementation in LNCaP-xenograft mouse significantly reduced tumour progression in these animals [99].

Additional studies further discovered that gamma-tocotrienol stimulated apoptosis of prostate carcinoma cells by causing under-expression of TGFβ2, NF-κB, EGFR, Fyn/HIF-1α and Id genes, concurrent with the stimulation of the JNK signalling pathway [98, 101, 103]. Fascinatingly, gamma-tocotrienol carried out its anti-invasive effect by inhibiting mesenchymal markers and significantly improving the expression of E-cadherin andβ -catenin [103]. It has also been published that gamma-tocotrienol increasingly attenuated the expression of prostate cancer stem cells (CSC) markers CD133/CD44, which are thought to be the main cause of remission in androgenindependent prostate cancer [102]. Moreover, tocotrienols were found to degrade the sterol regulatory element-binding protein-2 (SREBP-2) in prostate cancer cells, thereby reducing their viability through reduced cholesterol level [100].

Correspondingly, TRF also illustrated its chemopreventive and therapeutic activities against prostate cancer by inducing cell cycle arrest and apoptosis studies involving cell lines [104]. Furthermore, daily supplementation of TRF to transgenic adenocarcinoma mouse prostate mouse model (TRAMP) significantly suppressed tumour formation and high-grade neoplastic lesions due to the overexpression of pro-apoptotic proteins Bcl-2 antagonist of cell death (BAD), caspase-3 and CDK inhibitors (p21 and p27) [134].
