ABSTRACT
Melanoma is one of the most common skin infections, has triggered significant morbidity and mortality across the globe. Previous studies have reported that mutations in CDKN2A signalling network is associated with cutaneous malignant melanoma. In the present study, initially, the BioGrid database was utilized, and then hierarchical clustering was performed to identify the CDKN2A signature pathways. In addition, a GO Enrichment analysis was investigated using DAVID (n=187 genes) toolkit. Subsequently, the cBioPortal cancer genomic platform was exploited using alteration ranked frequency to determine the role of the CDKN2A signaling network in 363 samples of cutaneous malignant melanoma patients and we find that CDKN2A and its close interactors PTEN and HUWE1 show highest mutations. Further, we systematically employed molecular docking approach via MOE to target PTEN, CDKN2A and HUWE1 with chloroquine which is naturally occurring in medicinal plant Nigella sativa (NS) and observed virtuous interactions between all receptors and ligand molecules with a binding energy of -11.379, -10.324 and -9.06 Kcal/mol, respectively. The outcomes obtained stipulate a vigorous research resource for using chloroquine as a multitargeted anticancer drug. This novel evidence should help the development of effective therapeutic compounds for the treatment of cancer. Our results reveal that chloroquine is a relevant and novel potential therapeutic drug for the treatment of melanoma.
