Miconazole Nanoemulsions to Treat Melanoma: A Study of Formulation Development, Droplet Size and Solubility

Amado, Joana; Pires, Patrícia C.; Veiga, Francisco José; Paiva‐Santos, Ana Cláudia

doi:10.3390/ecmc2022-13416

Cited by 1 publication

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“…In a study published in 2019, we demonstrated for the first time that miconazole may exert a strong antimelanoma effect in vitro; we related such an effect, at least in part, to the expression of an ion channel, namely KCNN2 (28). Miconazole antimelanoma effect was then confirmed in a zebrafish model study published in 2020 [43], and miconazole nanoemulsions are under investigation as a possible formulation [44]. Mechanisms underlying the strong miconazole antimelanoma effect are still to be elucidated.…”

Section: Discussionmentioning

confidence: 85%

Anti-Melanoma Effects of Miconazole: Investigating the Mitochondria Involvement

Scatozza,

Giardina,

Valente

et al. 2024

IJMS

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Miconazole is an antimycotic drug showing anti-cancer effects in several cancers. However, little is known on its effects in melanoma. A375 and SK-MEL-28 human melanoma cell lines were exposed to miconazole and clotrimazole (up to 100 mM). Proliferation, viability with MTT assay and vascular mimicry were assayed at 24 h treatment. Molecular effects were measured at 6 h, namely, ATP-, ROS-release and mitochondria-related cytofluorescence. A metabolomic profile was also investigated at 6 h treatment. Carnitine was one of the most affected metabolites; therefore, the expression of 29 genes involved in carnitine metabolism was investigated in the public platform GEPIA2 on 461 melanoma patients and 558 controls. After 24 h treatments, miconazole and clotrimazole strongly and significantly inhibited proliferation in the presence of 10% serum on either melanoma cell lines; they also strongly reduced viability and vascular mimicry. After 6 h treatment, ATP reduction and ROS increase were observed, as well as a significant reduction in mitochondria-related fluorescence. Further, in A375, miconazole strongly and significantly altered expression of several metabolites including carnitines, phosphatidyl-cholines, all amino acids and several other small molecules, mostly metabolized in mitochondria. The expression of 12 genes involved in carnitine metabolism was found significantly modified in melanoma patients, 6 showing a significant impact on patients’ survival. Finally, miconazole antiproliferation activity on A375 was found completely abrogated in the presence of carnitine, supporting a specific role of carnitine in melanoma protection toward miconazole effect, and was significantly reversed in the presence of caspases inhibitors such as ZVAD-FMK and Ac-DEVD-CHO, and a clear pro-apoptotic effect was observed in miconazole-treated cells, by FACS analysis of Annexin V-FITC stained cells. Miconazole strongly affects proliferation and other biological features in two human melanoma cell lines, as well as mitochondria-related functions such as ATP- and ROS-release, and the expression of several metabolites is largely dependent on mitochondria function. Miconazole, likely acting via carnitine and mitochondria-dependent apoptosis, is therefore suggested as a candidate for further investigations in melanoma treatments.

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Section: Discussionmentioning

confidence: 85%