Chelerythrine chloride induces apoptosis in renal cancer HEK-293 and SW-839 cell lines.
Previous studies have demonstrated that the benzo[c]phenanthridine alkaloid chelerythrine chloride (CC) has inhibitory effects on various tumors. However, the anticancer activity of CC and its underlying mechanisms have not been elucidated in renal cancer cells. The present study examined the effects of CC on growth inhibition and apoptosis of renal cancer cellsin vitroandin vivo. Flow cytometry and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays revealed that CC markedly suppressed the growth of HEK-293 and human renal cancer SW-839 cells in a time- and dose-dependent manner. The xenograft mouse model, which was performed in nude mice, exhibited a reduced tumor growth following CC treatment. In addition, the present study revealed that CC significantly decreased the phosphorylation of extracellular signal-regulated kinase (ERK) and Akt, which was accompanied by upregulation of p53, B-cell lymphoma 2 (Bcl-2)-associated X protein, cleaved caspase-3 and cleaved poly (adenosine diphosphate-ribose) polymerase (PARP), and downregulation of Bcl-2, caspase-3 and PARP. Furthermore, the use of PD98059, a specific mitogen-activated protein kinase kinase inhibitor, potentiated the proapoptotic effects of CC, which indicated that CC may induce apoptosis in renal cancer cells partly via inhibition of ERK activity. Overall, the results of the present study demonstrated that CC may be developed as a potential anticancer treatment for patients with renal cancer.
Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, Henan 450000, P.R. China.
Xiao-Meng
XM
Chen
Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, Henan 450000, P.R. China.
Meng
M
Zhang
Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, Henan 450000, P.R. China.
Peng-Li
PL
Fan
Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, Henan 450000, P.R. China.
Yu-Hua
YH
Qin
Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, Henan 450000, P.R. China.
Hong-Wei
HW
Zhao
apoptosis; chelerythrine chloride; renal cancer