FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Chem Biol Interact / In vitro anticancer activity of Betulinic acid and derivativ...
Chemico-biological interactions2016; 246; 20-29; doi: 10.1016/j.cbi.2016.01.002

In vitro anticancer activity of Betulinic acid and derivatives thereof on equine melanoma cell lines from grey horses and in vivo safety assessment of the compound NVX-207 in two horses.

Abstract: Betulinic acid, a pentacyclic triterpene, and its derivatives are promising compounds for cancer treatment in humans. Melanoma is not only a problem for humans but also for grey horses as they have a high potential of developing melanoma lesions coupled to the mutation causing their phenotype. Current chemotherapeutic treatment carries the risk of adverse health effects for the horse owner or the treating veterinarian by exposure to antineoplastic compounds. Most treatments have low prospects for systemic tumor regression. Thus, a new therapy is needed. In this in vitro study, Betulinic acid and its two derivatives B10 and NVX-207, both with an improved water solubility compared to Betulinic acid, were tested on two equine melanoma cell lines (MelDuWi and MellJess/HoMelZh) and human melanoma (A375) cell line. We could demonstrate that all three compounds especially NVX-207 show high cytotoxicity on both equine melanoma cell lines. The treatment with these compounds lead to externalization of phosphatidylserines on the cell membrane (AnnexinV-staining), DNA-fragmentation (cell cycle analysis) and activation of initiator and effector caspases (Caspase assays). Our results indicate that the apoptosis is induced in the equine melanoma cells by all three compounds. Furthermore, we succeed in encapsulating the most active compound NVX-207 in 2-Hydroxyprolyl-β-cyclodextrine without a loss of its activity. This formulation can be used as a promising antitumor agent for treating grey horse melanoma. In a first tolerability evaluation in vivo the formulation was administered every one week for 19 consecutive weeks and well tolerated in two adult melanoma affected horses.
Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Get Full Text
Publication Date: 2016-01-07 PubMed ID: 26772157DOI: 10.1016/j.cbi.2016.01.002Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigates the anti-cancer effects of Betulinic acid and its derivatives B10 and NVX-207 on two types of equine melanoma cells, and also assesses the safe usage of NVX-207 in living horses. The study found positive results in cell death in the tested equine melanoma cell lines, and the most potent compound, NVX-207, was well tolerated when administered to horses with melanoma over a consecutive 19-week period.

Study Context and Objectives

  • The study’s context is based on two main factors – the high risk of developing melanoma lesions in grey horses and the need for safer melanoma therapeutic treatment that doesn’t expose horse owners or treating veterinarians to harmful antineoplastic compounds.
  • The main aim of this study is to find out if Betulinic acid and its two derivatives, B10 and NVX-207, can potentially offer a safer and effective cancer treatment option for equine melanoma.

Methodology and Results

  • The methods used in this experiment involve testing the cytotoxicity of Betulinic acid and its derivatives on two equine melanoma cells (MelDuWi and MellJess/HoMelZh) and a human melanoma (A375) cell line.
  • The results show that all three compounds, especially NVX-207, have high cell toxicity on the equine melanoma cell lines. The treatment with these compounds results in externalization of phosphatidylserines on the cell membrane (AnnexinV-staining), DNA-fragmentation (cell cycle analysis), and activation of initiator and effector caspases (Caspase assays), which are all signals of induced apoptosis or programmed cell death.

NVX-207 Formulation and In Vivo Testing

  • The next part of the study took the compound with the highest activity, NVX-207, and ensconced it in 2-Hydroxyprolyl-β-cyclodextrine without losing its efficacy. This encapsulated formulation can potentially be used as an anti-tumor agent for treating grey horse melanoma.
  • In tests with two adult melanoma-affected horses, the NVX-207 formulation was delivered every week for 19 consecutive weeks. The treatment was well tolerated in both horses, suggesting that NVX-207 can be a safe and effective treatment option for equine melanoma.

Cite This Article

APA
Liebscher G, Vanchangiri K, Mueller T, Feige K, Cavalleri JM, Paschke R. (2016). In vitro anticancer activity of Betulinic acid and derivatives thereof on equine melanoma cell lines from grey horses and in vivo safety assessment of the compound NVX-207 in two horses. Chem Biol Interact, 246, 20-29. https://doi.org/10.1016/j.cbi.2016.01.002

Publication

Chemico-biological interactions
ISSN: 1872-7786
NlmUniqueID: 0227276
Country: Ireland
Language: English
Volume: 246
Pages: 20-29
PII: S0009-2797(16)30002-3

Researcher Affiliations

Liebscher, G
  • Biozentrum, Martin Luther University Halle-Wittenberg, Weinbergweg 22, D-06120 Halle, Germany.
Vanchangiri, K
  • Biozentrum, Martin Luther University Halle-Wittenberg, Weinbergweg 22, D-06120 Halle, Germany.
Mueller, Th
  • Department of Hematology/ Oncology, Martin-Luther-University of Halle-Wittenberg, Halle/ Saale, Germany.
Feige, K
  • University of Veterinary Medicine Hannover, Foundation, Clinic for Horses, Bünteweg 9, 30559 Hannover, Germany.
Cavalleri, J-M V
  • University of Veterinary Medicine Hannover, Foundation, Clinic for Horses, Bünteweg 9, 30559 Hannover, Germany.
Paschke, R
  • Biozentrum, Martin Luther University Halle-Wittenberg, Weinbergweg 22, D-06120 Halle, Germany. Electronic address: reinhard.paschke@biozentrum.uni-halle.de.

MeSH Terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Caspases / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Enzyme Activation / drug effects
  • Female
  • Horses
  • Humans
  • Melanoma / pathology
  • Pentacyclic Triterpenes
  • Propanolamines / adverse effects
  • Propanolamines / chemistry
  • Propanolamines / pharmacology
  • Safety
  • Triterpenes / adverse effects
  • Triterpenes / chemistry
  • Triterpenes / pharmacology
  • Xenograft Model Antitumor Assays
  • Betulinic Acid

Citations

This article has been cited 19 times.
  1. Gielecińska A, Kciuk M, Mujwar S, Celik I, Kołat D, Kałuzińska-Kołat Ż, Kontek R. Substances of Natural Origin in Medicine: Plants vs. Cancer. Cells 2023 Mar 23;12(7).
    doi: 10.3390/cells12070986pubmed: 37048059google scholar: lookup
  2. Lombrea A, Semenescu AD, Magyari-Pavel IZ, Turks M, Lugiņina J, Peipiņš U, Muntean D, Dehelean CA, Dinu S, Danciu C. Comparison of In Vitro Antimelanoma and Antimicrobial Activity of 2,3-Indolo-betulinic Acid and Its Glycine Conjugates. Plants (Basel) 2023 Mar 9;12(6).
    doi: 10.3390/plants12061253pubmed: 36986941google scholar: lookup
  3. Pimenta J, Prada J, Cotovio M. Equine Melanocytic Tumors: A Narrative Review. Animals (Basel) 2023 Jan 10;13(2).
    doi: 10.3390/ani13020247pubmed: 36670786google scholar: lookup
  4. Yi Z, Gao Y, Yu F, Zhu Y, Liu H, Li J, Murua Escobar H. Interventions for treatment of cutaneous melanoma in horses: a structured literature review. Vet Res Commun 2023 Jun;47(2):347-360.
    doi: 10.1007/s11259-022-10023-8pubmed: 36329228google scholar: lookup
  5. Matias M, Pinho JO, Penetra MJ, Campos G, Reis CP, Gaspar MM. The Challenging Melanoma Landscape: From Early Drug Discovery to Clinical Approval. Cells 2021 Nov 9;10(11).
    doi: 10.3390/cells10113088pubmed: 34831311google scholar: lookup
  6. Weber LA, Delarocque J, Feige K, Kietzmann M, Kalbitz J, Meißner J, Paschke R, Cavalleri JV. Effects of Topically Applied Betulinic Acid and NVX-207 on Melanocytic Tumors in 18 Horses. Animals (Basel) 2021 Nov 13;11(11).
    doi: 10.3390/ani11113250pubmed: 34827981google scholar: lookup
  7. Coricovac D, Dehelean CA, Pinzaru I, Mioc A, Aburel OM, Macasoi I, Draghici GA, Petean C, Soica C, Boruga M, Vlaicu B, Muntean MD. Assessment of Betulinic Acid Cytotoxicity and Mitochondrial Metabolism Impairment in a Human Melanoma Cell Line. Int J Mol Sci 2021 May 4;22(9).
    doi: 10.3390/ijms22094870pubmed: 34064489google scholar: lookup
  8. Weber LA, Funtan A, Paschke R, Delarocque J, Kalbitz J, Meißner J, Feige K, Kietzmann M, Cavalleri JV. In vitro assessment of triterpenoids NVX-207 and betulinyl-bis-sulfamate as a topical treatment for equine skin cancer. PLoS One 2020;15(11):e0241448.
    doi: 10.1371/journal.pone.0241448pubmed: 33151949google scholar: lookup
  9. Weber LA, Meißner J, Delarocque J, Kalbitz J, Feige K, Kietzmann M, Michaelis A, Paschke R, Michael J, Pratscher B, Cavalleri JV. Betulinic acid shows anticancer activity against equine melanoma cells and permeates isolated equine skin in vitro. BMC Vet Res 2020 Feb 5;16(1):44.
    doi: 10.1186/s12917-020-2262-5pubmed: 32024502google scholar: lookup
  10. Fernandes J, de Amorim GC, da Veiga TE, Cardoso J, Arruda AC, Arruda MSP, Castelo-Branco MTL. Allantoin reduces cell death induced by cisplatin: possible implications for tumor lysis syndrome management. J Biol Inorg Chem 2019 Jun;24(4):547-562.
    doi: 10.1007/s00775-019-01661-6pubmed: 31030325google scholar: lookup
  11. Spivak A, Khalitova R, Nedopekina D, Dzhemileva L, Yunusbaeva M, Odinokov V, D'yakonov V, Dzhemilev U. Synthesis and Evaluation of Anticancer Activities of Novel C-28 Guanidine-Functionalized Triterpene Acid Derivatives. Molecules 2018 Nov 16;23(11).
    doi: 10.3390/molecules23113000pubmed: 30453551google scholar: lookup
  12. Shen H, Liu L, Yang Y, Xun W, Wei K, Zeng G. Betulinic Acid Inhibits Cell Proliferation in Human Oral Squamous Cell Carcinoma via Modulating ROS-Regulated p53 Signaling. Oncol Res 2017 Aug 7;25(7):1141-1152.
    doi: 10.3727/096504017X14841698396784pubmed: 28109089google scholar: lookup
  13. Koltai T, Fliegel L. Anoikis: To Die or Not to Die?. Int J Mol Sci 2026 Jan 6;27(2).
    doi: 10.3390/ijms27020579pubmed: 41596231google scholar: lookup
  14. Ungureanu Similie D, Bora L, Chiriac SD, Avram Ș, Minda D, Lugiņina J, Kroškins V, Turks M, Magyari-Pavel IZ, Dinu Ș, Dehelean CA, Danciu C. Uncovering New Antimelanoma Strategies: Experimental Insights into Semisynthetic Pentacyclic Triterpenoids. Life (Basel) 2025 Dec 10;15(12).
    doi: 10.3390/life15121884pubmed: 41465825google scholar: lookup
  15. Dangroo NA, Moussa Z, Alluhaibi MS, Alsimaree AA, Hawsawi MB, Alsantali RI, Singh J, Gupta N, S M B, Karunakar P, Mir JM, Rather MA, Ahmed SA. Novel C-3 and C-20 derived analogs of betulinic acid as potent cytotoxic agents: design, synthesis, in vitro and in silico studies. RSC Adv 2025 May 6;15(19):15164-15177.
    doi: 10.1039/d5ra01038apubmed: 40343306google scholar: lookup
  16. Narayan S, Krishna G, Mishra R. Bioactive Compound Chemistry and Antiasthmatic Activity of Betulinic Acid and Taraxerol in Experimental Models. Curr Top Med Chem 2025;25(25):2952-2968.
    doi: 10.2174/0115680266358488250421012523pubmed: 40325532google scholar: lookup
  17. Nemli E, Saricaoglu B, Kirkin C, Ozkan G, Capanoglu E, Habtemariam S, Sharifi-Rad J, Calina D. Chemopreventive and Chemotherapeutic Potential of Betulin and Betulinic Acid: Mechanistic Insights From In Vitro, In Vivo and Clinical Studies. Food Sci Nutr 2024 Dec;12(12):10059-10069.
    doi: 10.1002/fsn3.4639pubmed: 39723067google scholar: lookup
  18. Zscherpe P, Kalbitz J, Weber LA, Paschke R, Mäder K, von Rechenberg B, Cavalleri JV, Meißner J, Klein K. Potent drug delivery enhancement of betulinic acid and NVX-207 into equine skin in vitro - a comparison between a novel oxygen flow-assisted transdermal application device and microemulsion gels. BMC Vet Res 2024 May 16;20(1):202.
    doi: 10.1186/s12917-024-04064-1pubmed: 38755639google scholar: lookup
  19. Bache M, Heise NV, Thiel A, Funtan A, Seifert F, Petrenko M, Güttler A, Brandt S, Mueller T, Vordermark D, Thondorf I, Csuk R, Paschke R. Combination of Betulinic Acid Fragments and Carbonic Anhydrase Inhibitors-A New Drug Targeting Approach. Pharmaceutics 2024 Mar 14;16(3).
    doi: 10.3390/pharmaceutics16030401pubmed: 38543295google scholar: lookup
Subscribe to our newsletter
Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.