Modulation of cell growth and apoptosis response in human prostate cancer cells supplemented with tocotrienols

Abstract

Previous studies have shown that tocotrienols are powerful growth inhibitors and potent inducers of apoptosis in human breast cancer cells. The objective of the current study was to examine effects of tocotrienols on apoptotic signals in androgen-independent PC-3 human prostate cancer cells. We investigated the effects of the tocotrienol-rich fraction (TRF) from palm oil, a-tocopherol (aT), a-tocotrienol (aT 3 ), g-tocotrienol (gT 3 ) and d-tocotrienol (dT 3 ) on PC-3 cell growth. TRF inhibited PC-3 growth with a nonlinear response, with complete growth suppression at 10 mg/mL. dT 3 and gT 3 showed complete cell inhibition at 8 mg/mL whilst aT had no effect. dT 3 and gT 3 showed the most promise in the cell growth assays, and all subsequent experiments were performed with dT 3 , TRF and aT. TRF and dT 3 at 8 mg/mL induced apoptosis in PC-3 cells after 48 h of treatment. In addition, TRF and dT 3 treatments were able to affect the cell cycle, with accumulation in the S phase, G2 phase block and increases in SubG1 by 72 h. We then proceeded to investigate the expression levels of Fas receptor and Fas ligand, caspase 8, caspase 3 and bax in PC-3 cells following treatment with tocotrienols using real-time PCR and Western blot methods. TRF and dT 3 at 8 mg/mL increased Fas ligand expression levels by 368 and 456%, respectively, after 24 h and Fas receptor expression levels by 210% and 356%, respectively, after 48 h. TRF-and dT 3 -treated PC-3 cells overexpressed caspase 8 and bax protein after 24 h, and caspase 3 after 48 h. In conclusion, tocotrienols are able to induce apoptosis and cell cycle arrest in PC-3 cells, with increased expression of Fas receptor, Fas ligand, caspase 8, caspase 3 and bax, suggesting a potential role in chemoprevention of prostate cancer.

Tocotrienols Suppress Proinflammatory Markers and Cyclooxygenase‐2 Expression in RAW264.7 Macrophages

“…On top of that, studies are beginning to strengthen the notion that tocotrienols are superior to tocopherols in many aspects. TRF and individual tocotrienols, in particular d-and cT 3, are potent anti-proliferative agents, being able to induce apoptosis and cell cycle arrest in PC-3, a human prostate cancer cell line [43]. aT and aT 3 show no effect in that context.…”

The 21st Century Form of Vitamin E - Tocotrienol

“…TRF affects the cell cycle, with accumulation in S-phase, G2 phase block and increase in sub-G1 phase [75]. In HT-29 cells, tocotrienol arrests cell cycle in G0-G1 phase by downregulating Bcl -2, upregulating Bax and activating caspase 3 [76].…”

Research advancements in palm oil nutrition

“…Accumulation of tocotrienols in tissue imparts tremendous health benefits . Tocotrienols could help reduce blood cholesterol and arteriosclerotic functions , encompass possible anti‐angiogenic functions , exhibit efficient antioxidant activity as well as anticancer anti‐inflammatory effects , prevention of arthritis , prevention of osteoporosis , prevention of skin diseases , anti‐diabetic , and neuroprotective properties .…”