γ-Tocotrienol Inhibits Proliferation and Induces Apoptosis via the Mitochondrial Pathway in Human Cervical Cancer HeLa Cells

gamma-Tocotrienol, a kind of isoprenoid phytochemical, has antitumor activity. However, there is limited evidence that it has an effect on cervical cancer. In this study, the capacity to inhibit proliferation and induce apoptosis in human cervical cancer HeLa cells and the mechanism underlying these effects were examined. The results indicated that a gamma-tocotrienol concentration over 30 mu M inhibited the growth of HeLa cells with a 50% inhibitory concentration (IC50) of 46.90 +/- 3.50 mu M at 24 h, and significantly down-regulated the expression of proliferative cell nuclear antigen (PCNA) and Ki-67. DNA flow cytometric analysis indicated that gamma-tocotrienol arrested the cell cycle at G0/G1 phase and reduced the S phase in HeLa cells. gamma-tocotrienol induced apoptosis of HeLa cells in a time- and dose-dependent manner. gamma-tocotrienol-induced apoptosis in HeLa cells was accompanied by down-regulation of Bcl-2, up-regulation of Bax, release of cytochrome from mitochondria, activation of caspase-9 and caspase-3, and subsequent poly (ADP-ribose) polymerase (PARP) cleavage. These results suggested that gamma-tocotrienol could significantly inhibit cell proliferation through G0/G1 cell cycle arrest, and induce apoptosis via the mitochondrial apoptotic pathway in human cervical cancer HeLa cells. Thus, our findings revealed that gamma-tocotrienol may be considered as a potential agent for cervical cancer therapy.