title: 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: Department of Urology, Qilu Hospital of Shandong University, Ji'nan, Shandong, China; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.
authors: Zhiqing
authors: Z
authors: Fang
authors: Department of Urology, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.
authors: Yueqing
authors: Y
authors: Tang
authors: Department of Urology, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.
authors: Wei
authors: W
authors: Jiao
authors: Department of Urology, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.
authors: Zhaoquan
authors: Z
authors: Xing
authors: Department of Urology, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.
authors: Zhaoxin
authors: Z
authors: Guo
authors: Department of Urology, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.
authors: Weichang
authors: W
authors: Wang
authors: Department of Urology, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.
authors: Zhonghua
authors: Z
authors: Xu
authors: Department of Urology, Qilu Hospital of Shandong University, Ji'nan, Shandong, China; School of Nursing, Shandong University, Ji'nan, Shandong, China. Electronic address: zhaoxvl@sdu.edu.cn.
authors: Zhaoxu
authors: Z
authors: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053119:Benzophenanthridines / Q000494:pharmacology*; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays
chemical_list: D053119:Benzophenanthridines; C013615:nitidine; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Apoptosis; ERK; Nitidine chloride; Renal cancer