TOCOTRIENOLS CAN SUPPORT
SUPPRESSION OF PROLIFERATION OF CANCER CELLS
INDUCTION OF APOPTOSIS IN CANCER CELLS
ANTI-INVASION AND CHEMOSENSITIZATION
Introduction to Prostate Cancer and TRFApart from skin cancer, prostate cancer is the most common cancer observed in men. Prostate cancer is the 2nd leading cause of cancer-related deaths in the United States.
The aim of this study was to find the isomer of Vitamin E which demonstrated the most potent anticancer activities in prostate cancer cells (PCa) and to decipher the molecular pathway responsible for this activity. This study demonstrated the incredible anticancer activities of the Gamma and Delta isoforms of Tocotrienols.
How does Tocotrienol-Rich Fraction (TRF) fight Prostate Cancer?In the study, it was observed that all the isomers of Vitamin E, especially Gamma-Tocotrienol significantly suppressed the proliferation of LNCaP and PC-3 cancer cells. Delta-Tocotrienol, on the other hand, showed incredible potency in suppressing the cell proliferation and growth of LNCaP cells. It was also observed that Gamma-Tocotrienols induced apoptosis in the LNCaP cells. The order of inhibitory effect was as follows, γ-T3>δ-T3>β-T3>γ-T>δ-T≈α-T3≈α-T≈β-T (where ‘T’ stands for Tocopherols and T3 stands for Tocotrienols). Evidently, Tocotrienols, especially the Delta and the Gamma isoforms showed many potent anticancer activities as compared to Tocopherols.
Gamma-Tocotrienols induced apoptosis by the activation of pro-caspases and the presence of the sub-G1 cell population. Investigation of the effects of TRF on the pro-survival genes demonstrated that the induced apoptosis or cell death was associated with the suppression of EGF-R, NF-kB, and Id family proteins (Id1 and Id3). Also, Gama-Tocotrienol treatment suppressed the mesenchymal markers and restored the E-cadherin and gamma-catenin expression, which was associated with suppression of cell invasion capability.
To conclude, the study and data showed that the antiproliferative effects of Gamma-Tocotrienols function through multiple-signaling pathways, and for the first time, the anti-invasion and chemosensitization effect of Gamma-Tocotrienols against PCa cells was observed.
Reference for the Study in detail:1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2600692/
4. Agarwal MK, Agarwal ML, Athar M, Gupta S. Tocotrienol-rich fraction of palm oil activates p53, modulates Bax/Bcl2 ratio, and induces apoptosis independent of cell cycle association. Cell Cycle. 2004;3:205–211. [PubMed] [Google Scholar]
5. Ahmad NS, Khalid BA, Luke DA, Ima Nirwana S. Tocotrienol offers better protection than tocopherol from free radical-induced damage of rat bone. Clin Exp Pharmacol Physiol. 2005;32:761–770. [PubMed] [Google Scholar]
6. Ahn KS, Sethi G, Krishnan K, Aggarwal BB. Gamma-tocotrienol inhibits the nuclear factor-kappaB signaling pathway through inhibition of receptor-interacting protein and TAK1 leading to suppression of antiapoptotic gene products and potentiation of apoptosis. J Biol Chem. 2007;282:809–820. [PubMed] [Google Scholar]
7. Albini A, Iwamoto Y, Kleinman HK, Martin GR, Aaronson SA, Kozlowski JM, McEwan RN. A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res. 1987;47:3239–3245. [PubMed] [Google Scholar]
8. Cano A, Perez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio MG, Portillo F, Nieto MA. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol. 2000;2:76–83. [PubMed] [Google Scholar]
9. Chu Q, Ling MT, Feng H, Cheung HW, Tsao SW, Wang X, Wong YC. A novel anticancer effect of garlic derivatives: inhibition of cancer cell invasion through the restoration of E-cadherin expression. Carcinogenesis. 2006;27:2180–2189. [PubMed] [Google Scholar]
10. Chowdhury S, Burbridge S, Harper PG. Chemotherapy for the treatment of hormone-refractory prostate cancer. Int J Clin Pract. 2007;61:2064–2070. [PubMed] [Google Scholar]
11. Conte C, Floridi A, Aisa C, Piroddi M, Floridi A, Galli F. Gamma-tocotrienol metabolism and antiproliferative effect in prostate cancer cells. Ann NY Acad Sci. 2004;1031:391–394. [PubMed] [Google Scholar]
12. Coppe JP, Itahana Y, Moore DH, Bennington JL, Desprez PY. Id-1 and Id-2 proteins as molecular markers for human prostate cancer progression. Clin Cancer Res. 2004;10:2044–2051. <[PubMed] <[Google Scholar]
13. Craft N, Chhor C, Tran C, Belldegrun A, DeKernion J, Witte ON, Said J, Reiter RE, Sawyers CL. Evidence for clonal outgrowth of androgen-independent prostate cancer cells from androgen-dependent tumors through a two-step process. Cancer Res. 1999;59:5030–5036. [PubMed] [Google Scholar]
14. Dhanalakshmi S, Singh RP, Agarwal C, Agarwal R. Silibinin inhibits constitutive and TNFalpha-induced activation of NF-kappaB and sensitizes human prostate carcinoma DU145 cells to TNFalpha-induced apoptosis. Oncogene. 2002;21:1759–1767. [PubMed] [Google Scholar]
15. Eitsuka T, Nakagawa K, Miyazawa T. Down-regulation of telomerase activity in DLD-1 human colorectal adenocarcinoma cells by tocotrienol. Biochem Biophys Res Commun. 2006;348:170–175. [PubMed] [Google Scholar]
16. Feldman BJ, Feldman D. The development of androgen-independent prostate cancer. Nat Rev Cancer. 2001;1:34–45. [PubMed] [Google Scholar]
17. Ghosh A, Wang X, Klein E, Heston WD. Novel role of prostate-specific membrane antigen in suppressing prostate cancer invasiveness. Cancer Res. 2005;65:727–731. [PubMed] [Google Scholar]