Abstract
BackgroundEquine malignant melanoma (EMM) is a frequently occurring dermoepidermal tumor in grey horses. Currently available therapies are either challenging or inefficient. Betulinic acid (BA), a naturally occurring triterpenoid, is a promising compound for cancer treatment. To evaluate the potential of BA as a topical therapy for EMM, its anticancer effects on primary equine melanoma cells and dermal fibroblasts and its percutaneous permeation through isolated equine skin were assessed in vitro.ResultsBA showed antiproliferative and cytotoxic effects on both primary equine melanoma cells and fibroblasts in a time- and dose-dependent manner. The lowest half-maximal inhibitory concentrations were obtained 96 h after the beginning of drug exposure (12.7 μmol/L and 23.6 μmol/L for melanoma cells eRGO1 and MelDuWi, respectively, in cytotoxicity assay). High concentrations of the compound were reached in the required skin layers in vitro.ConclusionBA is a promising substance for topical EMM treatment. Further clinical studies in horses are necessary to assess safety and antitumoral effects in vivo.
Highlights
Equine malignant melanoma (EMM) is a frequently occurring dermoepidermal tumor in grey horses
PriFi1 and PriFi2 stained positive for vimentin (Fig. 1), whereas no signal was detected after incubation with anti-cytokeratin
Reported Half-maximal inhibitory concentration (IC50) values of equine melanoma cells determined by the sulforhodamine B assay (33.1 μmol/L (MelDuWi) and 33.4 μmol/L (MelJess)) [23] were higher than the ones investigated in the present study by MTS assay (23.6 μmol/L (MelDuWi) and 12.7 μmol/L) after the same duration of incubation (96 h) with Betulinic acid (BA)
Summary
Equine malignant melanoma (EMM) is a frequently occurring dermoepidermal tumor in grey horses. Betulinic acid (BA), a naturally occurring triterpenoid, is a promising compound for cancer treatment. To evaluate the potential of BA as a topical therapy for EMM, its anticancer effects on primary equine melanoma cells and dermal fibroblasts and its percutaneous permeation through isolated equine skin were assessed in vitro. Betulinic acid (BA), a naturally occurring pentacyclic triterpenoid in the bark of plane and birch trees, has been demonstrated to exert a variety of biological features. Its antitumor effects are mediated mainly by a CD95- and p53-independent induction of apoptosis [11]. Equine malignant melanoma (EMM) is a common skin neoplasm in aging grey horses [24,25,26].
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