Gamma-Tocotrienol inhibits proliferation of human chronic myeloid leukemic cells via activation of extrinsic and intrinsic apoptotic pathways

Tocotrienols and tocopherols are natural forms of vitamin E that existin four isoforms (alpha, beta, gamma and delta). Gamma-tocotrienolisreported to possess many anti-cancer effects including anti-proliferativeand pro-apoptotic activities. To date, the effects of treating K562, ahuman chronic myeloid leukemic cell line with gamma-tocotrienolis notwell documented. The anti-cancer and pro-apoptotic effects of gammatocotrienol on the K562 cells were evaluated using cell-based assays. Theeffect of gamma-tocotrienol exposure of the expression of genes relatedto apoptosis was determined using a commercial quantitative real-timepolymerase chain reaction array annotated with primers related tohuman apoptosis. The expression of some of the differentially expressedgenes and proteins were confirmed using quantitative polymerasechain reaction technology and enzyme-linked immunosorbent assay,respectively. Treatment with gamma-tocotrienol induced effectivecytotoxicity in the K562 cells mainly via the apoptosis pathway. Geneexpression studies using the quantitative polymerase chain reactionarray approach showed that gamma-tocotrienol induced expression ofseveral pro-apoptotic genes related to the BCL-2, the death receptorand the Caspase families in the K562 CML cells. Gamma-tocotrienol isa potent inducer of apoptosis in K562 chronic myeloid leukemic cellsvia the intrinsic and extrinsic apoptotic pathways. It has the potentialof being developed as a therapeutic agent for chronic myeloid leukemia.Further studies using experimental models or clinical studies arewarranted to support these findings.