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Ketamine and dodecyl maltoside synergy as a potential topical therapeutic approach for melanoma
Sourour Idoudi1, Hadeel Kheraldine2, Gazala Anamangadan3
1Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar. si1602796@qu.edu.qa.
Abstract:
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.
Insights
Ketamine combined with dodecyl maltoside shows promise for melanoma treatment. This combination effectively reduced melanoma cell viability and promoted apoptosis, while remaining safe for normal cells.
Area of Science:
- Oncology
- Pharmacology
- Dermatology
Background:
- Melanoma, an aggressive skin cancer, presents limited therapeutic options due to resistance and toxicity.
- Ketamine (KET), an anesthetic, exhibits potential anticancer properties.
- Dodecyl maltoside (DDM) is a permeation enhancer that may improve drug delivery.
Purpose of the Study:
- To investigate the combined anticancer effects of ketamine and dodecyl maltoside on melanoma cells.
- To evaluate the safety of the KET+DDM combination in normal fibroblasts.
- To explore the underlying mechanisms of KET+DDM-induced cell death.
Main Methods:
- MDA-MB-435 melanoma cells and normal fibroblasts (NFBs) were treated with KET and KET+DDM.
- Assays included cell viability, IC50 determination, apoptosis, cell cycle distribution, migration, and colony formation.
- Protein expression was analyzed using Western blot.
Main Results:
- The KET+DDM combination significantly reduced melanoma cell viability compared to KET alone, with no observed toxicity in NFBs.
- This combination induced significant apoptosis, G2/M cell cycle arrest, and inhibited cell migration and colony formation.
- Western blot indicated altered expression of apoptosis-related proteins (Bax, Bcl-xl, p53, Caspase-8).
Conclusions:
- Ketamine, particularly when formulated with DDM, demonstrates potential as a topical therapeutic strategy for melanoma.
- The KET+DDM combination may induce apoptosis via caspase-independent pathways, requiring further investigation.
- In vivo studies are necessary to confirm the clinical applicability of this combination therapy.
