A naturally occurring acid extracted from the bark of plane and birch trees shows early promise as a potential externally applied treatment for melanomas in horses, researchers report.
Lisa Weber and her colleagues, writing in the journal BMC Veterinary Research, set out to learn about the effects of betulinic acid on equine melanoma cells.
Melanomas are common in ageing grey horses, with current therapies either challenging or inefficient.
Betulinic acid is a naturally occurring triterpenoid, a family of plant-produced compounds that have a role in their self-defense mechanisms.
It is considered a promising compound on several levels. It has been shown to have anti-HIV, antiparasitic and anti-inflammatory properties. The substance has also shown anticancer activity.
The German and Austrian study looked into the acid’s potential as a topical therapy for equine malignant melanoma, exploring its anticancer effects on primary equine melanoma cells and healthy dermal fibroblasts — cells within the skin responsible for generating connective tissue and allowing the skin to recover from injury.
Betulinic acid’s ability to permeate through equine skin in a laboratory setting was also assessed in the University of Veterinary Medicine Hannover, Foundation, study.
They found that betulinic acid showed antiproliferative and cytotoxic effects on both primary equine melanoma cells and fibroblasts in a time and dose-dependent manner.
“With increasing treatment duration, cell proliferation and cell viability decreased significantly.”
“However, the results show that normal equine dermal fibroblasts are also sensitive to betulinic acid in the concentrations investigated.”
In human studies, results have been somewhat different. Human melanocytes, dermal fibroblasts and peripheral blood lymphocytes proved to be more resistant to a betulinic treatment than cancer cells.
“Even if normal equine skin cells are affected by local betulinic acid treatment, inflammatory reactions are suspected to be minor,” the study team said.
“Nevertheless, to gain more insights about the therapeutic potential of betulinic acid, the safety and efficacy of the compound have to be addressed on healthy and melanoma affected equine skin in vivo (in live animals).”
High concentrations of the compound penetrated the required skin layers for melanoma treatment in lab tests in combination with triglycerides, raising the possibility that the acid could be applied directly to skin for treatment.
“Betulinic acid is a promising substance for topical equine malignant melanona treatment,” the researchers concluded, even though selectivity to cancer cells over normal cells could not be demonstrated.
“In essence, this study supports the use of betulinic acid in further preclinical and clinical trials for topical equine malignant melanoma treatment.”
The full study team comprised Lisa Weber, Jessica Meißner, Julien Delarocque, Jutta Kalbitz, Karsten Feige, Manfred Kietzmann, Anne Michaelis, Reinhard Paschke, Julia Michael, Barbara Pratscher and Jessika-M. V. Cavalleri, from a range of German and Austrian institutions.
Weber, L.A., Meißner, J., Delarocque, J. et al. Betulinic acid shows anticancer activity against equine melanoma cells and permeates isolated equine skin in vitro. BMC Vet Res 16, 44 (2020). https://doi.org/10.1186/s12917-020-2262-5