Ketamine and dodecyl maltoside synergy as a potential topical therapeutic approach for melanoma.

Melanoma is the most aggressive subtype of skin cancer with limited treatment options due to toxicity and therapy resistance. This study investigates the anticancer potential of ketamine (KET), an anesthetic recently reported to have anticancer effects, in combination with dodecyl maltoside (DDM), a permeation enhancer that may improve drug delivery. The effects of KET and KET + DDM were evaluated in MDA-MB-435 melanoma cells via cell viability, IC₅₀ determination, apoptosis, cell cycle distribution, migration, colony formation, and protein expression studies. Normal fibroblasts were used to assess safety. Compared to KET alone, the KET + DDM combination significantly reduced the viability of MDA-MB-435 cells while maintaining safety in NFBs. This combination also promoted significant apoptosis, induced cell cycle arrest at the G2/M phase, and inhibited migration and colony formation, while maintaining safety in normal fibroblasts Western blot analysis revealed upregulation of Bax and downregulation of Bcl-xl, p53, and Caspase-8, suggesting a mechanism of apoptosis. These findings demonstrate that KET, particularly when combined with DDM, holds promise as a potential topical therapeutic strategy against melanoma. It is suggested that KET + DDM might promote apoptosis through alternative, caspase-independent pathways, underscoring the need for further mechanistic studies. Further in vivo studies are warranted to validate its clinical applicability.