Evidence of γ-Tocotrienol as an Apoptosis-Inducing, Invasion-Suppressing, and Chemotherapy Drug – Sensitizing Agent in Human Melanoma Cells
Nutrition and Cancer, 61(3), 357–366
DOI: 10.1080/01635580802567166
Copyright © 2009, Taylor & Francis Group, LLC
ISSN: 0163-5581 print / 1532-7914 online
Version of record first published: 16 Apr 2009
Abstract:
To date, the most effective cure for metastatic melanoma re-mains the surgical resection of the primary tumor. Recently, tocotrienol-rich-fraction has shown antiproliferative effect on can-cer cells. To elucidate this anticancer property in malignant melanoma, this study aimed, first, to identify the most potent iso-mer for eliminating melanoma cells and second to decipher the molecular pathway responsible for its activity. Results showed that the inhibitory effect of gamma-tocotrienol was most potent, which resulted in induction of apoptosis as evidenced by activation of pro-caspases and the accumulation of sub-G1 cell population. Examina-tion of the prosurvival genes revealed that the gamma-tocotrienol-induced cell death was associated with suppression of NF-kappaB, EGF-R, and Id family proteins. Meanwhile, gamma-tocotrienol treatment also resulted in induction of JNK signaling pathway, and inhibition of JNK activity by selective inhibitor was able to par-tially block the effect of gamma-tocotrienol. Interestingly, gamma-tocotrienol treatment led to suppression of mesenchymal markers and the restoration of E-cadherin and gamma-catenin expression, which was associated with suppression of cell invasion capabil-ity. Furthermore, synergistic effect was observed when cells were cotreated with gamma-tocotrienol and chemotherapy drugs. To-gether, our results demonstrated for the first time the anti-invasion and chemonsensitization effect of gamma-tocotrienol against hu-man malignant melanoma cells.
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