Nitidine chloride inhibits renal cancer cell metastasis via suppressing AKT signaling pathway

• Published in: Food and chemical toxicology 2013-10, Vol.60, p.246-251
• Main Authors: Fang, Zhiqing, Tang, Yueqing, Jiao, Wei, Xing, Zhaoquan, Guo, Zhaoxin, Wang, Weichang, Shi, Benkang, Xu, Zhonghua, Liu, Zhaoxu
• Format: Article
• Language: English
• Subjects: AKT; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Benzophenanthridines - pharmacology; Biological and medical sciences; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Down-Regulation; Humans; kidney neoplasms; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Kidneys; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Medical sciences; Metastasis; MMP; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); neoplasm cells; Neoplasm Metastasis; Nephrology. Urinary tract diseases; Nitidine chloride; Phosphorylation; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Renal cancer; signal transduction; Signal Transduction - drug effects; Toxicology; Tumors; Tumors of the urinary system
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2013.07.062

•We evaluated the anti-metastasis effect of NC in human renal cancer cells.•NC down-regulates the levels of MMP-2/-9 in NC-treated renal cancer cells.•NC inhibited renal cancer cell metastasis by AKT-dependent pathway.•NC is potentially for further renal cancer therapy. Nitidine Chloride (NC) has been shown to have anti-cancer effects on various tumors. However, whether NC could exert anti-metastasis activity in renal cancer cells and the underlying mechanisms have not been elucidated. In this work, our data demonstrated the anti-metastasis effects of NC on renal cancer cells in vitro. With scratch assay and transwell assays, we found that NC potently suppressed the migration and invasion of 786-O and A498 cells. Mechanistically, we presented that NC significantly decreased phosphorylation of AKT, accompanied by down-regulation of MMP-2 and MMP-9. Furthermore, a specific AKT inhibitor, LY294002, could enhance the anti-metastasis effects of NC, which indicated that NC suppressed metastasis of renal cancer cells partly via inhibition of AKT activity. Taken together, our results imply that NC can be developed as a potential anti-metastasis agent to renal cancer.