Abstract
BackgroundRenal cell carcinoma (RCC) is one of the tumors most refractory to chemotherapy to date. Therefore, novel therapeutic agents are urgently needed for this disease. Capsaicin (CPS), a natural active ingredient of green and red peppers, and a ligand of transient receptor potential vanilloid type 1 (TRPV1), has been showed potential in suppression of tumorigenesis of several cancers. Nonetheless, the anti-cancer activity of CPS has never been studied in human RCC.MethodsCCK8 analysis, LDH release activity and ROS generation analysis, flow cytometry analysis, and nuclear staining test were performed to test the influence of CPS in cultured cells in vitro, meanwhile western blot was done to uncover the precise molecular mechanisms. 786-O renal cancer xenografts were builded to investigate the antitumor activity of CPS in vivo.ResultsWe found treatment of CPS reduced proliferation of renal carcinoma cells, which could be attenuated by TRPV1 representative antagonist capsazepine (CPZ). CPS induced obvious apoptosis in renal carcinoma cells. These events were associated with substantial up-regulation of pro-apoptotic genes including c-myc, FADD, Bax and cleaved-caspase-3, -8, and -9, while down-regulation of anti-apoptotic gene Bcl2. Besides, CPS-treatment activated P38 and JNK MAPK pathways, yet P38 and JNK inhibitors afforded protection against CPS-induced apoptosis by abolishing activation of caspase-3, -8, and -9. Furthermore, CPS significantly slowed the growth of 786-O renal cancer xenografts in vivo.ConclusionsSuch results reveal that CPS is an efficient and potential drug for management of human RCC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2831-y) contains supplementary material, which is available to authorized users.
Highlights
Renal cell carcinoma (RCC) is one of the tumors most refractory to chemotherapy to date
CPS significantly slowed the growth of 786-O renal cancer xenografts in vivo
Such results reveal that CPS is an efficient and potential drug for management of human RCC
Summary
Renal cell carcinoma (RCC) is one of the tumors most refractory to chemotherapy to date. Capsaicin (CPS), a natural active ingredient of green and red peppers, and a ligand of transient receptor potential vanilloid type 1 (TRPV1), has been showed potential in suppression of tumorigenesis of several cancers. The anti-cancer activity of CPS has never been studied in human RCC. As the most common type of kidney cancer, renal cell carcinoma (RCC) is a worldwide public concern. Human RCC accounts for 2 to 3 % of all cancers, and approximately 90 % of kidney cancer, with an increasing incidence of diagnosis (representing 200,000 patients diagnosed per year worldwide) [1]. Transient receptor potential vanilloid type 1 (TRPV1) is a nonselective, ligand-gated cationic channel which can be regulated by thermal, mechanical and chemical stimuli such as CPS [5]. TRPV1 was found to play important physiologic and pathological roles in renal, and its activation would make much improvement in acute and chronic renal diseases [9, 10]
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