文章基本信息

标题：A Redox-Inactive Derivative of Tocotrienol Suppresses Tumor Growth of Mesothelioma Cells in a Xenograft Model
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作者：Ayami Sato ; Tsunetaka Arai ; Momoka Fusegi 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2019
卷号：42
期号：6
页码：1034-1037
DOI：10.1248/bpb.b18-00924
出版社：The Pharmaceutical Society of Japan
摘要：Malignant mesothelioma (MM) is an aggressive cancer with poor prognosis. We focused on the anticancer activity of tocotrienol (T3) and have reported that a new redox-inactive T3 derivative (6- O -carboxypropyl-α-tocotrienol; T3E) exerts stronger inhibitory effects on MM cell growth than that of T3 in vitro . Furthermore, we have revealed some mechanisms of T3E that are involved in anti-MM effects. However, the effect of T3E in vivo remains unclear. In this study, we compared the plasma concentrations of T3E to that of T3 using mice to clarify differences in pharmacokinetics. Blood was sequentially collected after oral administration of T3 or T3E, and plasma concentrations were analyzed by HPLC. The area under the plasma T3 and T3E concentration–time curve from 0 to 24 h ( AUC 0–24 h) of T3E was two times higher than that of T3. In addition, we evaluated the effect of T3E oral administration on tumor growth using a xenograft model of mice that were transplanted with human MM cells (H2052 cell line). Tumor volume was significantly reduced without body weight loss in mice orally administered 150 mg/kg T3E once per 2 d for 10 d, which suggests that T3E has potential anti-MM effects.
关键词：tocotrienol derivative;plasma concentration;malignant mesothelioma