The Enhancing Effect Of Gamma-Cyclodextrin Inclusion On Gamma-Tocotrienol-Dependent Negative Growth Control Of Mesothelioma Cells In A Xenograft Model

Background: Malignant mesothelioma is an aggressive cancer with no effective treatment options. Of phytochemicals, tocotrienol (T3), a member of vitamin E, is one of the most potent anti- mesothelioma agents, but the effectiveness in vivo is quite limited, due to its low bioavailability. In this study, we investigated if the oral treatment of gamma - T3 inclusion with gamma - cyclodextrin (CD) could improve the bioavailability and anticancer activity of the T3.Findings: Using nude mice bearing MSTO- 211H cells (a human malignant mesothelioma cell line), the effect of gamma - T3 inclusion with gamma - CD on gamma - T3 level in tumor tissues, tumor growth, and its related mRNA levels were examined. The difference of tumor growth between the two groups had no statistical significance, but the latter showed a lower tendency compared with the former. In linked with this observation, the level of vascular endothelial growth factor mRNA required for in vivo tumor growth in gamma - T3 inclusion with gamma - CD group was lower than that in gamma - T3 group, on the contrary, the level of gamma - T3 level showed an opposite tendency.Conclusion: Our study demonstrated that the bioavailability of gamma - T3 was improved by an oral administration of a novel gamma - T3 inclusion complex with CD. Furthermore, the improvement of the bioavailability contributed to the increase of anticancer activity of gamma - T3 in vivo.