Previous studies reported that
norcantharidin (NCTD) has anti-
tumor effects. We investigated the antitumor effects and underlying mechanism of NCTD on human
renal cancer in vitro and in vivo. NCTD significantly decreased
renal cancer cell viability by induction of apoptosis, as determined by the MTT assay and
annexin V/PI staining. NCTD treatment of 786-O and A-498 cells altered the expression of
caspase family
proteins and PARP. Moreover, NCTD induced mitochondrial depolarization, which was accompanied by an increased level of Bax and decreased levels of Bcl-2 and Mcl-1. NCTD induced endoplasmic reticulum (ER) stress by increasing the expression of
Grp78, p-elF2α, ATF4, and CHOP. Pretreatment with an ER stress inhibitor (
salubrinal) significantly attenuated the effect of NCTD. NCTD also induced activation of the AKT pathway in 786-O and A-498 cells. Overexpression of AKT partly reversed the effect of NCTD on apoptosis. NCTD treatment led to decreased expression of Bcl-2 and Mcl-1, and increased expression of Bax, cleaved-caspase-9, cleaved-PARP, and p-elF2α. Our in vivo studies demonstrated that NCTD significantly inhibited
tumor growth in a nude mouse xenograft model. Taken together, our results suggest that NCTD is a potential anti-
tumor agent for treatment of
renal carcinoma.