Author:
Zhang Yunjing,Wang Shiwen,Chen Yukun,Zhang Junqian,Yang Jing,Xian Jingrong,Li Lihui,Zhao Hu,Hoffman Robert M.,Zhang Yanmei,Jia Lijun
Abstract
Esophageal squamous cell carcinoma (ESCC) is a recalcitrant cancer. The Chinese herbal monomer fangchinoline (FCL) has been reported to have anti-tumor activity in several human cancer cell types. However, the therapeutic efficacy and underlying mechanism on ESCC remain to be elucidated. In the present study, for the first time, we demonstrated that FCL significantly suppressed the growth of ESCC both in vitro and in vivo. Mechanistic studies revealed that FCL-induced G1 phase cell-cycle arrest in ESCC which is dependent on p21 and p27. Moreover, we found that FCL coordinatively triggered Noxa-dependent intrinsic apoptosis and DR5-dependent extrinsic apoptosis by transactivating ATF4, which is a novel mechanism. Our findings elucidated the tumor-suppressive efficacy and mechanisms of FCL and demonstrated FCL is a potential anti-ESCC agent.
Funder
Innovative Research Group Project of the National Natural Science Foundation of China
Shanghai Municipal Education Commission
Program of Shanghai Academic Research Leader
Cited by
8 articles.
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