Nitidine chloride induces apoptosis and inhibits tumor cell proliferation via suppressing ERK signaling pathway in renal cancer.

Abstract

Nitidine chloride (NC), a natural bioactive alkaloid derived from Zanthoxylum nitidum (Roxb) DC, has been shown to have inhibitory effects on various tumors. However, whether NC could exert anti-cancer activity and the underlying mechanisms have not been elucidated in renal cancer cells. In this study, we demonstrated the growth inhibitory and pro-apoptotic effects of NC on renal cancer cells both in vitro and in vivo. With cell viability and flow cytometric apoptosis assays, we found that NC potently suppressed the growth of 786-O and A498 cells in a time- and dose- dependent manner. Consistently, the xenograft model performed in nude mice exhibited reduced tumor growth with NC treatment. Mechanically, we presented that NC significantly decreased phosphorylation of ERK and Akt, accompanied by up-regulation of P53, Bax, cleavage caspase-3 and cleavage PARP, downregulation of Bcl-2, caspase-3 and PARP. Furthermore, a specific MEK inhibitor, PD98059, could potentiate the pro-apoptotic effects of NC, which indicated that NC might trigger apoptosis in renal cancer cells partly via inhibition of ERK activity. Taken together, our results imply that NC could be developed as a potential anticancer agent to renal cancer and worthy of further studies.

• Authors: Zhiqing Fang, Yueqing Tang, Wei Jiao, Zhaoquan Xing, Zhaoxin Guo, Weichang Wang, Zhonghua Xu, Zhaoxu Liu
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 66 Pg. 210-6 (Apr 2014) ISSN: 1873-6351 [Electronic] England
• PMID: 24508476 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Benzophenanthridines
• nitidine
• Extracellular Signal-Regulated MAP Kinases

Topics

• Animals
• Apoptosis (drug effects)
• Benzophenanthridines (pharmacology)
• Cell Line, Tumor
• Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors, metabolism)
• Humans
• Kidney Neoplasms (enzymology, pathology)
• Mice
• Mice, Nude
• Xenograft Model Antitumor Assays