TY - JOUR
T1 - Boesenberols, Pimarane Diterpenes with TRAIL-Resistance-Overcoming Activity from Boesenbergia pandurata
AU - Karmakar, Utpal K.
AU - Ishikawa, Naoki
AU - Arai, Midori A.
AU - Ahmed, Firoj
AU - Koyano, Takashi
AU - Kowithayakorn, Thaworn
AU - Ishibashi, Masami
N1 - Funding Information:
This study was supported by KAKENHI Grant Number 23102008 from MEXT, 26305001 and 26293022 from JSPS, the Uehara Memorial Foundation, and the Tokyo Biochemical Research Foundation (TBRF)
Publisher Copyright:
© 2016 The American Chemical Society and American Society of Pharmacognosy.
PY - 2016/8/26
Y1 - 2016/8/26
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.jnatprod.6b00424
DO - 10.1021/acs.jnatprod.6b00424
M3 - Article
C2 - 27508308
AN - SCOPUS:84984704748
SN - 0163-3864
VL - 79
SP - 2075
EP - 2082
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 8
ER -
