Palm Tocotrienols Inhibit Proliferation of Murine Mammary Cancer Cells and Induce Expression of lnterleukin-24 mRNA

Several mechanisms have been postulated for the anticancer effects of tocotrienols. In this study, for the first time, the anticancer effect of tocotrienols is linked to increased expression of interleukin-24 (IL-24) mRNA, a cytokine reported to have antitumor effects in many cancer models. Tocotrienol isomers ( alpha -T3, gamma -T3, and delta -T3) and tocotrienol-rich fraction (TRF) inhibited the growth of the 4T1 murine mammary cancer cells (P < 0.05), with IC sub(50) values 8.99,4.79,3.73, and 8.63 mu /mL, respectively. Tumor incidence and tumor load in TRF-supplemented BALB/c mice was decreased by 57.1% and 93.6% (P < 0.05), respectively. The induction of the IL-24 mRNA in the 4T1 cells by vitamin E decreased in the following order: delta -T3 > gamma -T3 > TRF > alpha -T3 > alpha -T, which was similar to their antiproliferative effects. The IL-24 mRNA levels in tumor tissues of BALB/c mice supplemented with TRF increased 2-fold when compared with control mice. Increased levels of IL-24 have been associated with inhibition of tumor growth and angiogenesis. Treatment of 4T1 cells with TRF and delta -T3 significantly decreased IL-8 and vascular endothelial growth factor mRNA levels. Hence, we report that tocotrienols have potent anti-angiogenic and antitumor effects that is associated with increased levels of IL-24 mRNA.