In vitro assessment of triterpenoids NVX-207 and betulinyl-bis-sulfamate as a topical treatment for equine skin cancer.
Administration, Topical
Animals
Apoptosis
/ drug effects
Cell Cycle
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Dermis
/ pathology
Diffusion
Fibroblasts
/ drug effects
Horse Diseases
/ drug therapy
Horses
Inhibitory Concentration 50
Propanolamines
/ pharmacology
Skin Neoplasms
/ drug therapy
Sulfonic Acids
/ pharmacology
Triterpenes
/ administration & dosage
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
01
05
2020
accepted:
14
10
2020
entrez:
5
11
2020
pubmed:
6
11
2020
medline:
29
12
2020
Statut:
epublish
Résumé
Equine sarcoid (ES) is the most prevalent skin tumor in equids worldwide. Additionally, aging grey horses frequently suffer from equine malignant melanoma (EMM). Current local therapies targeting these skin tumors remain challenging. Therefore, more feasible topical treatment options should be considered. In order to develop a topical therapy against ES and EMM, betulinyl-bis-sulfamate and NVX-207, derivatives of the naturally occurring betulin and betulinic acid, respectively, were evaluated for their antiproliferative (crystal violet staining assay), cytotoxic (MTS assay) and apoptotic (AnnexinV staining, cell cycle investigations) effects on primary ES cells, EMM cells and equine dermal fibroblasts in vitro. The more potent derivative was assessed for its in vitro penetration and permeation on isolated equine skin within 30 min and 24 h using Franz-type diffusion cells and HPLC analysis. Betulinyl-bis-sulfamate and NVX-207 inhibited the proliferation and metabolism in ES cells, EMM cells and fibroblasts significantly (p < 0.001) in a time- and dose-dependent manner. NVX-207 had superior anticancer effects compared to betulinyl-bis-sulfamate. Both compounds led to the externalization of phosphatidylserines on the cell membrane and DNA fragmentation, demonstrating that the effective mode of action was apoptosis. After 48 h of treatment with NVX-207, the number of necrotic cells was less than 2% in all cell types. Detected amounts of NVX-207 in the different skin layers exceeded the half-maximal inhibitory concentrations calculated by far. Even though data obtained in vitro are auspicious, the results are not unconditionally applicable to the clinical situation. Consequently, in vivo studies are required to address the antitumoral effects of topically applied NVX-207 in ES and EMM patients.
Identifiants
pubmed: 33151949
doi: 10.1371/journal.pone.0241448
pii: PONE-D-20-12654
pmc: PMC7643960
doi:
Substances chimiques
2-amino-3-hydroxy-2-hydroxymethylpropyl 3-acetylbetulinoate
0
Propanolamines
0
Sulfonic Acids
0
Triterpenes
0
sulfamic acid
9NFU33906Q
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0241448Déclaration de conflit d'intérêts
The authors declare that no competing interests exist. The affiliation "BioSolutions Halle GmbH” of Dr. Jutta Kalbitz does not alter our adherence to PLOS ONE policies on sharing data and materials. As described in the Funding Statement, BioSolutions Halle GmbH is not a commercial funder, but an equal partner in the TopiDrugHorse project.
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