Boesenberols, Pimarane Diterpenes with TRAIL-Resistance-Overcoming Activity from Boesenbergia pandurata

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• 作者：Utpal K. Karmakar ; Naoki Ishikawa ; Midori A. Arai ; Firoj Ahmed ; Takashi Koyano ; Thaworn Kowithayakorn ; Masami Ishibashi
• 刊名：Journal of Natural Products
• 出版年：2016
• 出版时间：August 26, 2016
• 年：2016
• 卷：79
• 期：8
• 页码：2075-2082
• 全文大小：392K
• 年卷期：0
• ISSN：1520-6025

文摘

TRAIL is a potent and selective inducer of apoptosis in most cancer cells while sparing normal cells, which makes it an attractive target for the development of new cancer therapies. In a screening program on natural resources with the ability to abrogate TRAIL resistance, the bioassay-guided fractionation of Boesenbergia pandurata rhizomes resulted in the isolation of 17 pimarane diterpenes and a monoterpene. Among these, compounds 1–8, named boesenberols A–H, are new pimarane diterpenes. All compounds exhibited TRAIL-resistance-overcoming activity in TRAIL-resistant AGS cells. Subtoxic doses of the major compound 9 sensitized AGS cells to TRAIL-induced apoptosis by up-regulating apoptosis-inducing proteins, such as DR4, DR5, p53, Fas, CHOP, Bak, and cleaved caspases-3, -8, and -9, and down-regulating the levels of cell survival proteins, such as Bcl-2, c-FLIP, and GSK-3β, in TRAIL-resistant AGS cells. Furthermore, compound 9 did not decrease the viability of noncancerous (HEK293) cells at concentrations up to 30 μM.