Chapter 4 – Role of Tocotrienols in Chemosensitization of Cancer

Abstract Chemotherapy is one of the standard methods of treatment in many cancers. However, most of the tumors develop resistance to chemotherapeutic agents leading to recurrence, metastasis, and ultimately death of the patients. Therefore, a strategy to overcome chemoresistance and sensitize tumor cells to antitumor agents is urgently required. One promising strategy is to use dietary nutraceutical that sensitizes tumors to the chemotherapeutics. Tocotrienols are unsaturated vitamin E nutraceuticals found in fruits, vegetables, cereal grains, and essential oils and have potent antitumor activities without any clinical toxicity. In this monograph, we discussed the role of tocotrienols in chemosensitization of tumors to chemotherapeutic agents. The tumors sensitized by tocotrienols are pancreatic, breast, lung, colorectal, gastric, prostate, melanoma, bladder, hepatic, malignant mesothelioma, and multiple myeloma. The chemotherapeutic agents used are gemcitabine, capecitabine, tamoxifen, paclitaxel/docetaxel, doxorubicin/epirubicin, cisplatin, erlotinib/gefitinib, thalidomide/bortezomib, Met inhibitor, TRAIL, autophagy inducer, celecoxib, and statins. The chemosensitization of tumor cells by tocotrienols is mediated through modulating multiple signaling molecules such as cell proliferative proteins, cell survival proteins, nuclear factor-kappa B (NF-κB), signal transducer and activator of transcription-3 (STAT-3), HMG-CoA reductase, growth factor receptor, and apoptosis signaling pathways. These studies suggest that tocotrienols are promising agents used to sensitize tumors to standard chemotherapeutics. Future studies should be focused on both the efficacy and the safety of tocotrienols used in combination with chemotherapeutic agents in cancer patients.