Derivatives of betulin and betulinic acid have shown promise against equine skin tumor cells in a laboratory experiment.
Betulinic acid is the oxidation product of betulin and can be extracted from various botanical sources.
Lisa Annabel Weber and her colleagues in the German study noted that early studies had demonstrated betulinic acid’s anti-tumor activity against human melanoma and other malignancies in cell culture and in animal models.
Treatment with the acid kills the cancer cells due to a direct effect on the mitochondria.
The scientists, most of whom were affiliated with the University of Veterinary Medicine Hannover and Martin-Luther-University Halle-Wittenberg, noted that equine sarcoids are the most prevalent skin tumors in horses.
Additionally, aging grey horses frequently develop equine malignant melanomas.
Current local therapies targeting these skin tumors remain challenging.
The study team set out to determine whether derivatives from betulin and betulinic acid showed any promise as a topical treatment option against these two tumor types. They also monitored their effects on equine dermal fibroblasts.
The betulin derivative tested in the lab setting was betulinyl-bis-sulfamate, while the betulinic acid derivative was NVX-207.
Both derivatives were found to inhibit the proliferation and metabolism in the sarcoid cells, melanoma cells and fibroblasts significantly in a time and dose-dependent manner.
“NVX-207 had superior anti-cancer effects compared to betulinyl-bis-sulfamate,” the study team reported in the open-access journal PLOS ONE.
Because of this, the compound was used for further permeation studies, where it was demonstrated that high concentrations could be reached in isolated equine skin in the lab setting.
After 48 hours of treatment of tissue samples, the number of necrotic cells was less than 2% in all cell types.
The authors described the findings as auspicious but stressed that they were not unconditionally applicable in a clinical situation.
Studies in live horses with sarcoids and melanomas are required to more fully assess the anti-tumor effects of topically applied NVX-207, they said.
Because the anti-cancer effects were shown to be concentration and time-dependent, prospective treatment regimens in horses with short application intervals and long treatment durations could favorably influence the concentration and effectiveness of NVX-207 in horses with skin tumors.
The study team comprised Weber, Julien Delarocque, Jessica Meißner, Karsten Feige and Manfred Kietzmann, all with the University of Veterinary Medicine Hannover; Anne Funtan and Reinhard Paschke, with Martin-Luther-University Halle-Wittenberg; Jessika-Maximiliane Cavalleri, with the University of Veterinary Medicine Vienna; and Jutta Kalbitz, with BioSolutions Halle GmbH.
Weber LA, Funtan A, Paschke R, Delarocque J, Kalbitz J, Meißner J, et al. (2020) In vitro assessment of triterpenoids NVX-207 and betulinyl-bis-sulfamate as a topical treatment for equine skin cancer. PLoS ONE 15(11): e0241448. https://doi.org/10.1371/journal.pone.0241448