Ponicidin Induces Apoptosis of Murine Melanoma by Inhibiting the NF-κB Signaling Pathway

Abstract

Ponicidin (PON), a diterpenoid extracted from the Chinese herb Rubescens, has been reported to be a therapeutic cytotoxic drug for the treatment of various types of human cancers. According to the statistics, the incidence of malignant melanoma is increasing year by year and the degree of malignancy is extremely high, so early treatment is very important. In the present study, we demonstrated the antitumor effect of PON on melanoma in vitro and in vivo. Cell Counting Kit-8 (CCK-8) assay was used to detect cell proliferation rate, crystal violet staining and TdT-mediated dUTP Nick-End Labeling (TUNEL) kit was used to detect cell apoptosis, and Western blotting was used to detect the expression of apoptotic indicators and related signaling pathway proteins. Finally, the tumor-bearing mouse model was constructed. Treating melanoma B16F0 and B16F10 cells with different concentrations (10 and 20 µmol/L) of PON magnificantly decreased cell viability. In addition, PON significantly activates the expression of pro-apoptotic proteins, including cleaved-poly(ADP-ribose)polymerase (PARP) (cl.PARP), Bak and Bim proteins, and also inhibits the expression of anti-apoptotic protein Mcl-1 and nuclear transcription factor nuclear factor-kappaB (NF-κB) in melanoma cells. Lastly, PON effectively inhibits the growth of mouse xenografts in vivo. These results suggest that PON induces apoptosis of melanoma cells may be achieved by inhibiting NF-κB signal pathway, but the specific mechanism remains to be further elucidated. Taken together, PON may serve as an effective potential drug for the treatment of melanoma.