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.
Bibliographical noteFunding Information:
National Institutes of Health, Grant/Award Numbers: CA187027 and CA196639; National Natural Science Foundation of China, Grant/Award Number: 81572812; Key Program of Henan Province, China, Grant/Award Number: 161100510300
This work was supported by Key Program of Henan Province, China (Grant 161100510300) and National Natural Science Foundation of China (Grant 81572812) and grants from the National Institutes of Health (CA187027 and CA196639).
- gastric cancer