Kanga Rani Selvaduray
International Medical University, Malaysia
Title: Palm Tocotrienols Inhibit Proliferation of Murine Mammary Cancer Cells, Enhance Immune Response and Induce Expression of IL-24 mRNA
Biography
Biography: Kanga Rani Selvaduray
Abstract
Several mechanisms have been postulated for the anti-cancer effects of tocotrienols. In this study, the anti-cancer mechanism of tocotrienols is for the first time linked to increased expression of interleukin-24 (IL-24) mRNA, a cytokine reported to have anti-tumor effects in many cancer models. The anti-proliferative effects of tocotrienol-rich fraction (TRF) from palm oil, γ- and δ-tocotrienol (γ-T3 and δ-T3) and α-tocopherol (α-T) were studied on 4T1 murine mammary cancer cells. TRF, γ-T3 and δ-T3 significantly inhibited the growth of the 4T1 cells with IC50 values of 8.99, 4.79 and 3.73μg/ml respectively. Tumor incidence and tumor load in BALB/c mice were decreased by 57.1% and 93.6% respectively (p<0.05) with TRF supplementation. Tumourigenesis was examined and compared against control in both nude and BALB/c mice models. The mice were injected with MDA-MB-231 and 4T1 cells respectively for the different models, and were fed with TRF by oral gavage. This study shows that palm tocotrienols have strong inhibitory effects on the growth of both MDA-MB-231 and 4T1 cells both in vitro and in vivo. In addition the immune modulatory effects of tocotrienols were also investigated and it was found that TRF enhanced production of NK cells (P < 0.05) as well as IFN-γ (P < 0.05), which in turn regulate the immune protection against cancer cells. These observations were recorded in both mice models. The 4T1 cells treated with TRF, δ-T3 and α-T exhibited highest levels of IL-24 mRNA in δ-T3 treated cells, followed by TRF and α-T. The IL-24 mRNA levels in tumor tissues of BALB/c mice supplemented with TRF increased two-fold as compared to control mice. Increased levels of IL-24 have been associated with inhibition of tumor growth and angiogenesis. TRF and δ-T3 treated 4T1 cells significantly decreased IL-8 and vascular endothelial growth factor (VEGF) mRNA levels. We hereby report that the anti-tumor including the anti-angiogenic effects of tocotrienols are associated with increased levels of IL-24 mRNA.