Lapachone suppresses the proliferation of human malignant melanoma cells by targeting specificity protein 1

Abstract

lapachone (lap), a novel natural quinone derived from the bark of the Pink trumpet tree (Tabebuia avellanedae) has been demonstrated to have anticancer activity. In this study we investigated whether lap exhibits anti-proliferative effects on two human malignant melanoma (HMM) cell lines, G361 and SK-MEL-28. The effects of lap on the HMM cell lines were investigated using 3-(4,5-dimethylthiazol-2-yl)5-(3-carb oxymethoxyphenyl)2-(4-sulfophenyl-2H-tetrazolium (MTS) assay, 4',6-diamidino-2-phenylindole (DAPI) staining Annexin V and Dead cell assay, mitochondrial membrane potential (MMP) assay and western blot analysis. We demonstrated that lap significantly induced apoptosis and suppressed cell viability in the HMM cells. Intriguingly, the transcription factor specificity protein 1 (Sp1) was significantly downregulated by lap in a dose-and time-dependent manner. Furthermore, lap modulated the protein expression level of the Sp1 regulatory genes including cell cycle regulatory proteins and apoptosis-associated proteins. Taken together our findings indicated that lap modulates Sp1 transactivation and induces apoptotic cell death through the regulation of cell cycle-and apoptosis-associated proteins. Thus, lap may be used as a promising anticancer drug for cancer prevention and may improve the clinical outcome of patients with cancer.