Premium
Gossypin inhibits gastric cancer growth by direct targeting of AURKA and RSK2
Author(s) -
Wang Li,
Wang Xiangyu,
Chen Hanyong,
Zu Xueyin,
Ma Fayang,
Liu Kangdong,
Bode Ann M.,
Dong Zigang,
Kim Dong Joon
Publication year - 2019
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.6253
Subject(s) - apoptosis , cancer , cancer research , cell cycle , cyclin b1 , cancer cell , cell growth , cell cycle checkpoint , kinase , cyclin d1 , chemistry , phosphorylation , cyclin a , biology , cyclin dependent kinase 1 , microbiology and biotechnology , biochemistry , genetics
Gossypin is a flavone extracted from Hibiscus vitifolius , which has been reported to exhibit anti‐inflammatory, antioxidant, and anticancer activities. However, the anticancer properties of gossypin and its molecular mechanism of action against gastric cancer have not been fully investigated. In the present study, we report that gossypin is an Aurora kinase A (AURKA) and RSK2 inhibitor that suppresses gastric cancer growth. Gossypin attenuated anchorage‐dependent and anchorage‐independent gastric cancer cell growth as well as cell migration. Based on the results of in vitro screening and cell‐based assays, gossypin directly binds to and inhibits AURKA and RSK2 activities and their downstream signaling proteins. Gossypin decreased S phase and increased G2/M phase cell cycle arrest by reducing the expression of cyclin A2 and cyclin B1 and the phosphorylation of the CDC protein. Additionally, gossypin also induced intrinsic apoptosis by activating caspases and PARP and increasing the expression of cytochrome c . Our results demonstrate that gossypin is an AURKA and RSK2 inhibitor that could be useful for treating gastric cancer.