TY - JOUR
T1 - Triterpenes from Poria cocos are revealed as potential retinoid X receptor selective agonists based on cell and in silico evidence
AU - Xu, Hui
AU - Wang, Yuchen
AU - Zhao, Junnan
AU - Jurutka, Peter W.
AU - Huang, Dechun
AU - Liu, Liangyun
AU - Zhang, Lange
AU - Wang, Suilou
AU - Chen, Yadong
AU - Cheng, Shujie
N1 - Funding Information:
This study was supported by grants from the National Natural Science Foundation of China (31701595), National Key R&D Program of China (2017YFD0400203), Natural Science Foundation of Jiangsu Province (BK20160750) and College Students Innovation Project for the R&D of Novel Drugs (J1030830).
Publisher Copyright:
© 2020 John Wiley & Sons A/S.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Poria cocos is an edible and medicinal fungus that is widely used in Traditional Chinese Medicines as well as in modern applications. Retinoid X receptor (RXR) occupies a central place in nuclear receptor signaling, and a pharmacological RXR-dependent pathway is involved in myeloid cell function. Here, structural information for 82 triterpenes from P. cocos and 17 known RXR agonists was collected in a compound library and retrieved for a molecular docking study. Three triterpenes, 16α-hydroxytrametenolic acid (HTA), pachymic acid (PA), and polyporenic acid C (PPAC), were identified as novel RXR-specific agonists based on luciferase reporter assays and in silico evidence. Treatment with HTA, PA, and PPAC significantly induced differentiation of the human promyelocytic leukemia cell line HL-60 with EC50 values of 21.0 ± 0.52, 6.7 ± 0.37, and 9.4 ± 0.65 μM, respectively. These effects were partly blocked by the RXR antagonist UVI3003, suggesting that an RXR-dependent pathway may play an important role in their anti-acute promyelocytic leukemia (APL) effects. Taken together, triterpenes from P. cocos are revealed as naturally occurring RXR selective agonists with the potential for anti-cancer activity. These results suggest a novel approach to the treatment or prevention of APL.
AB - Poria cocos is an edible and medicinal fungus that is widely used in Traditional Chinese Medicines as well as in modern applications. Retinoid X receptor (RXR) occupies a central place in nuclear receptor signaling, and a pharmacological RXR-dependent pathway is involved in myeloid cell function. Here, structural information for 82 triterpenes from P. cocos and 17 known RXR agonists was collected in a compound library and retrieved for a molecular docking study. Three triterpenes, 16α-hydroxytrametenolic acid (HTA), pachymic acid (PA), and polyporenic acid C (PPAC), were identified as novel RXR-specific agonists based on luciferase reporter assays and in silico evidence. Treatment with HTA, PA, and PPAC significantly induced differentiation of the human promyelocytic leukemia cell line HL-60 with EC50 values of 21.0 ± 0.52, 6.7 ± 0.37, and 9.4 ± 0.65 μM, respectively. These effects were partly blocked by the RXR antagonist UVI3003, suggesting that an RXR-dependent pathway may play an important role in their anti-acute promyelocytic leukemia (APL) effects. Taken together, triterpenes from P. cocos are revealed as naturally occurring RXR selective agonists with the potential for anti-cancer activity. These results suggest a novel approach to the treatment or prevention of APL.
KW - Poria cocos
KW - Traditional Chinese Medicines
KW - acute promyelocytic leukemia
KW - naturally occurring agonist
KW - retinoid X receptor
KW - triterpenes
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U2 - 10.1111/cbdd.13610
DO - 10.1111/cbdd.13610
M3 - Article
C2 - 31444840
AN - SCOPUS:85073650208
SN - 1747-0277
VL - 95
SP - 493
EP - 502
JO - Chemical Biology and Drug Design
JF - Chemical Biology and Drug Design
IS - 5
ER -