The tocotrienol‐rich fraction from rice bran enhances cisplatin‐induced cytotoxicity in human mesothelioma H28 cells

• DOI: 10.1002/ptr.3107
• Publication Date: 2010-02-01T12:30:51Z
• Authors: Keisuke Nakashima; Nantiga Virgona; Mio Miyazawa; Takashi Watanabe; Tomohiro Yano
• Keywords: LY294002; Viability assay

Resistance to chemotherapy (chemoresistance) is a serious problem in malignant mesothelioma, highly aggressive neoplasm. Gamma-tocotrienol (gamma-T3) can sensitize various cancerous cells chemotherapeutic agents by inhibiting pathways that lead treatment resistance. In this study, we investigated the modulating effect of tocotrienol-rich fraction (TRF) from rice bran, which abundant gamma-T3, on chemoresistance human MM H28 cells. TRF caused marked reduction viability dose-dependent manner, while cisplatin had no cells, indicating are resistant cisplatin. A significant increase cytotoxicity was observed treated with TRF, and enhanced combination The cytotoxic closely related inhibition phosphatidylinositol 3-kinase (PI3K)-AKT signaling. Inactivation Akt signaling or mitigated cisplatin-induced activation Akt, resulting reducing Reduced cell attenuated against were also following use PI3K inhibitor, LY294002. These results suggest therapy plausible strategy for achieving tolerance agent therapy.