Betulinic acid shows anticancer activity against equine melanoma cells and permeates isolated equine skin in vitro

Weber, Lisa A.; Meißner, Jessica; Delarocque, Julien; Kalbitz, Jutta; Feige, Karsten; Kietzmann, Manfred; Paschke, Ralf; Michael, Julia; Pratscher, Barbara; Cavalleri, Jessika‐M. V.

doi:10.1186/s12917-020-2262-5

Cited by 21 publications

(45 citation statements)

References 58 publications

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“…Proliferation assay. The proliferation assay was performed as published [45]. Briefly, a modified crystal violet staining assay (CVS) was carried out to investigate the antiproliferative effects of BBS and NVX-207 on primary equine cells.…”

Section: Evaluation Of the Anticancer Effects Of Bbs And Nvx-207 On Ementioning

confidence: 99%

“…Cytotoxicity assay. The cytotoxicity of the compounds was assessed by the CellTiter 96 1 AQ ueous One Solution Cell Proliferation Assay (MTS) (Promega GmbH, Mannheim, Germany) as reported [45]. In brief, in order to reach cell confluence within 48 h, cells were seeded into 96-well plates in adequate densities (MelDuWi 30,000 cells/well; PriFi1, PriFi2, eRGO1 20,000 cells/well; sRGO1and sRGO2 15,000 cells/well).…”

Section: Plos Onementioning

confidence: 99%

“…Two different pharmaceutical formulations were provided by Skinomics GmbH, Halle, Germany, for in vitro permeation studies. Based on previous permeation studies with BA [45], test formulation 1 consisted of "Basiscreme DAC" (pharmaceutical PLOS ONE amphiphilic cream as published in the German Drug Codex) with 1% NVX-207 and 20% medium-chain triglycerides. The formulation was modified because of an inhomogenous distribution of NVX-207 in test formulation 1 (oily sediments and overall recovery rate < 50% in Franz-type diffusion cells (FDC) experiments): Test formulation 2 contained "Basiscreme DAC" with 1% NVX-207.…”

Section: Diffusion Of Nvx-207 Into Equine Skinmentioning

confidence: 99%

“…Promising substances for topical ES and EMM treatment could be triterpenoids, such as betulinic acid (BA) and its derivatives [45,46]. Betulinic acid, the oxidation product of betulin, is a pentacyclic lupane-type triterpenoid and can be extracted from various botanical sources [47].…”

Section: Introductionmentioning

confidence: 99%

“…effects of BA against EMM cells and its potent permeation in isolated equine skin have recently been reported [45]. However, based on a classification for the cytotoxicity of triterpenes [61], the half-maximal inhibitory concentrations (IC 50 ) of BA for EMM cells and other human and animal cancer cell lines are considered to be only moderate.…”

Section: Introductionmentioning

confidence: 99%

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In vitro assessment of triterpenoids NVX-207 and betulinyl-bis-sulfamate as a topical treatment for equine skin cancer

et al. 2020

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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.

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Section: Evaluation Of the Anticancer Effects Of Bbs And Nvx-207 On Ementioning

confidence: 99%

Section: Plos Onementioning

confidence: 99%

Section: Diffusion Of Nvx-207 Into Equine Skinmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In vitro assessment of triterpenoids NVX-207 and betulinyl-bis-sulfamate as a topical treatment for equine skin cancer

et al. 2020

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Enhanced Accumulation of Betulinic Acid in Transgenic Hairy Roots of Senna obtusifolia Growing in the Sprinkle Bioreactor and Evaluation of Their Biological Properties in Various Biological Models

Kowalczyk

Sitarek

Toma

et al. 2021

Chemistry & Biodiversity

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Betulinic acid, which is found in transgenic roots of Senna obtusifolia (L.) H.S.Irwin & Barneby, is a pentacyclic triterpene with distinctive pharmacological activities. In this study, we report the differences in the content of betulinic acid and selected anthraquinones in transgenic S. obtusifolia hairy roots with overexpression of the PgSS1 gene (SOPSS2 line) and in transformed hairy roots without this genetic construct (SOA41 line). Both hairy root lines grew in 10 L sprinkle bioreactor. Additionally, the extracts obtained from this plant material were used for biological tests. Our results demonstrated that the SOPSS2 hairy root cultures from the bioreactor showed an increase in the content of betulinic acid (38.125 mg/g DW), compared to the SOA41 hairy root line (4.213 mg/g DW). Biological studies have shown a cytotoxic and antiproliferative effect on U‐87MG glioblastoma cells, and altering the level of apoptotic proteins (Bax, p53, Puma and Noxa). Antimicrobial properties were demonstrated for both tested extracts, with a stronger effect of SOPSS2 extract. Moreover, both extracts showed moderate antiviral properties on norovirus surrogates.

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Betulinic acid: A natural promising anticancer drug, current situation, and future perspectives

Aswathy

Vijayan

Daimary

et al. 2022

J Biochem & Molecular Tox

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Natural products serve as the single most productive source for the discovery of drugs and pharmaceutical leads. Among the various chemicals derived from microbes, plants, and animals, phytochemicals have emerged as potential candidates for the development of anticancer drugs due to their structural diversities, complexities, and pleiotropic effects. Herein, we discuss betulinic acid (BA), a ubiquitously distributed lupane structured pentacyclic triterpenoid, scrutinized as a promising natural agent for the prevention, suppression, and management of various human malignancies. Ease of availability, common occurrences, cell‐specific cytotoxicity, and astonishing selectivity are the important factors that contribute to the development of BA as an anticancer agent. The current review delineates the mechanistic framework of BA‐mediated cancer suppression through the modulation of multiple signaling pathways and also summarizes the key outcomes of BA in preclinical investigations.

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Betulinic acid shows anticancer activity against equine melanoma cells and permeates isolated equine skin in vitro

Cited by 21 publications

References 58 publications

In vitro assessment of triterpenoids NVX-207 and betulinyl-bis-sulfamate as a topical treatment for equine skin cancer

In vitro assessment of triterpenoids NVX-207 and betulinyl-bis-sulfamate as a topical treatment for equine skin cancer

Enhanced Accumulation of Betulinic Acid in Transgenic Hairy Roots of Senna obtusifolia Growing in the Sprinkle Bioreactor and Evaluation of Their Biological Properties in Various Biological Models

Betulinic acid: A natural promising anticancer drug, current situation, and future perspectives

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