KEY TAKEAWAYS
- The study aimed to investigate the antitumor activity of miconazole and clotrimazole in human melanoma cell lines A375 and SK-MEL-28.
- Miconazole showed potential as a candidate for melanoma treatment due to its pro-apoptotic effects via carnitine and mitochondria.
While Miconazole demonstrates anticancer properties in various cancers, its impact on melanoma remains poorly understood.
Francesca Scatozza and the team aimed to investigate the effects of miconazole and clotrimazole on proliferation, viability, vascular mimicry, and molecular markers in A375 and SK-MEL-28 melanoma cell lines.
Researchers initiated exposure of A375 and SK-MEL-28 human melanoma cell lines to miconazole and clotrimazole (up to 100 mM). After 24 hours of treatment, they assessed proliferation and viability using the MTT assay and vascular mimicry. At the 6-hour mark, molecular effects such as ATP, ROS release, and mitochondria-related cytofluorescence were evaluated.
Additionally, they conducted a metabolomic profile analysis. Among the metabolites examined, carnitine was one of the most affected. Subsequently, they investigated the expression of 29 genes associated with carnitine metabolism using the public platform GEPIA2 in 461 melanoma patients and 558 controls.
After 24 hours of treatment, miconazole and clotrimazole significantly inhibited proliferation and reduced viability and vascular mimicry in both melanoma cell lines, even in the presence of 10% serum. Following 6 hours of treatment, there was a notable decrease in ATP levels and an increase in ROS, accompanied by a significant reduction in mitochondria-related fluorescence.
Miconazole strongly influenced the expression of various metabolites in A375 cells, including carnitines, phosphatidyl-cholines, and all amino acids, most of which are metabolized in mitochondria. Analysis revealed significant modifications in the expression of 12 genes related to carnitine metabolism in melanoma patients, with 6 genes significantly impacting patient survival.
In A375 cells, the antiproliferative effect of miconazole was completely nullified in the presence of carnitine, indicating a specific protective role of carnitine against miconazole’s impact on melanoma. Furthermore, the inhibition was significantly reversed in the presence of caspase inhibitors, such as ZVAD-FMK and Ac-DEVD-CHO, highlighting a clear pro-apoptotic effect of miconazole-treated cells as evidenced by FACS analysis of Annexin V-FITC stained cells.
Miconazole demonstrated a robust impact on proliferation and various biological characteristics in two human melanoma cell lines. Additionally, mitochondria-related functions were affected, including ATP and ROS release, while the expression of several metabolites was largely contingent on mitochondrial function.
Given its potential mechanism involving carnitine and mitochondria-dependent apoptosis, miconazole emerges as a promising candidate for further exploration in melanoma treatment research.
The study received financial support from the Grant Ric. Corr.3.4 by Ministry of Health to A.F.
Source: https://pubmed.ncbi.nlm.nih.gov/38612401/
Scatozza F, Giardina MM, Valente C, et al. (2024). “Anti-Melanoma Effects of Miconazole: Investigating the Mitochondria Involvement.” Int J Mol Sci. 2024 Mar 22;25(7):3589. doi: 10.3390/ijms25073589. PMID: 38612401; PMCID: PMC11011910.
