Betulinic acid shows anticancer activity against equine melanoma cells and permeates isolated equine skin in vitro.
Abstract: Equine malignant melanoma (EMM) is a frequently occurring dermoepidermal tumor in grey horses. Currently available therapies are either challenging or inefficient. Betulinic acid (BA), a naturally occurring triterpenoid, is a promising compound for cancer treatment. To evaluate the potential of BA as a topical therapy for EMM, its anticancer effects on primary equine melanoma cells and dermal fibroblasts and its percutaneous permeation through isolated equine skin were assessed in vitro. Results: BA showed antiproliferative and cytotoxic effects on both primary equine melanoma cells and fibroblasts in a time- and dose-dependent manner. The lowest half-maximal inhibitory concentrations were obtained 96 h after the beginning of drug exposure (12.7 μmol/L and 23.6 μmol/L for melanoma cells eRGO1 and MelDuWi, respectively, in cytotoxicity assay). High concentrations of the compound were reached in the required skin layers in vitro. Conclusions: BA is a promising substance for topical EMM treatment. Further clinical studies in horses are necessary to assess safety and antitumoral effects in vivo.
Publication Date: 2020-02-05 PubMed ID: 32024502PubMed Central: PMC7003431DOI: 10.1186/s12917-020-2262-5Google 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.
- 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.
The research article outlines a study on betulinic acid (BA), a naturally found compound, and its potential as a topical treatment for equine malignant melanoma (EMM), a common skin cancer in grey horses. The study examines the antiproliferative and cytotoxic effects of BA on equine melanoma cells and how it permeates through equine skin.
Objective of the Research
- The main goal of this research was to evaluate the efficacy of betulinic acid (BA) as a topical treatment for equine malignant melanoma (EMM). The researchers aimed to determine the effects of BA on equine melanoma cells and fibroblasts, and its potential skin absorption.
Methodology
- The researchers tested the impact of BA on primary equine melanoma cells and fibroblasts.
- They measured the effects in a time- and dose-dependent manner.
- The study also included an in vitro investigation of BA’s skin permeation capacities.
Results
- The study revealed that BA exhibited both antiproliferative and cytotoxic effects on the melanoma cells and fibroblasts.
- The effects were recorded as time- and dose-dependent, with the most significant impact seen 96 hours after initial drug exposure.
- The required skin layers showed a high concentration of the compound throughout the in vitro evaluation.
Conclusions
- The findings of this research considered BA to be a promising substance for the topical treatment of EMM.
- However, further research is required to understand its safety and anti-tumor effects in a live situation, necessitating more clinical studies on horses.
Cite This Article
APA
Weber LA, Meißner J, Delarocque J, Kalbitz J, Feige K, Kietzmann M, Michaelis A, Paschke R, Michael J, Pratscher B, Cavalleri JV.
(2020).
Betulinic acid shows anticancer activity against equine melanoma cells and permeates isolated equine skin in vitro.
BMC Vet Res, 16(1), 44.
https://doi.org/10.1186/s12917-020-2262-5 Publication
Researcher Affiliations
- Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559, Hannover, Germany.
- Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Foundation, Bünteweg 17, 30559, Hanover, Germany. Jessica.Meissner@tiho-hannover.de.
- Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559, Hannover, Germany.
- Biosolutions Halle GmbH, Weinbergweg 22, 06120, Halle (Saale), Germany.
- Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559, Hannover, Germany.
- Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Foundation, Bünteweg 17, 30559, Hanover, Germany.
- Biozentrum, Martin Luther University Halle-Wittenberg, Weinbergweg 22, 06120, Halle (Saale), Germany.
- Biozentrum, Martin Luther University Halle-Wittenberg, Weinbergweg 22, 06120, Halle (Saale), Germany.
- Skinomics GmbH, Weinbergweg 23, 06120, Halle (Saale), Germany.
- University Small Animal Clinic, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210, Vienna, Austria.
- University Equine Clinic, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210, Vienna, Austria.
- University Equine Clinic, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210, Vienna, Austria.
MeSH Terms
- Animals
- Antineoplastic Agents / pharmacokinetics
- Antineoplastic Agents / pharmacology
- Cell Line, Tumor
- Fibroblasts / drug effects
- Horse Diseases / drug therapy
- Horses
- Melanoma / drug therapy
- Melanoma / veterinary
- Pentacyclic Triterpenes
- Skin / drug effects
- Skin Neoplasms / drug therapy
- Skin Neoplasms / veterinary
- Triterpenes / pharmacokinetics
- Triterpenes / pharmacology
- Betulinic Acid
Conflict of Interest Statement
Manfred Kietzmann is a member of the editorial board of BMC Veterinary Research.
References
This article includes 63 references
- Kashiwada Y, Hashimoto F, Cosentino LM, Chen CH, Garrett PE, Lee KH. Betulinic acid and dihydrobetulinic acid derivatives as potent anti-HIV agents.. J Med Chem 1996 Mar 1;39(5):1016-7.
- Enwerem NM, Okogun JI, Wambebe CO, Okorie DA, Akah PA. Anthelmintic activity of the stem bark extracts of Berlina grandiflora and one of its active principles, Betulinic acid.. Phytomedicine 2001 Mar;8(2):112-4.
- Costa JF, Barbosa-Filho JM, Maia GL, Guimarães ET, Meira CS, Ribeiro-dos-Santos R, de Carvalho LC, Soares MB. Potent anti-inflammatory activity of betulinic acid treatment in a model of lethal endotoxemia.. Int Immunopharmacol 2014 Dec;23(2):469-74.
- Pisha E, Chai H, Lee IS, Chagwedera TE, Farnsworth NR, Cordell GA, Beecher CW, Fong HH, Kinghorn AD, Brown DM. Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis.. Nat Med 1995 Oct;1(10):1046-51.
- Kessler JH, Mullauer FB, de Roo GM, Medema JP. Broad in vitro efficacy of plant-derived betulinic acid against cell lines derived from the most prevalent human cancer types.. Cancer Lett 2007 Jun 18;251(1):132-45.
- Rzeski W, Stepulak A, Szymański M, Sifringer M, Kaczor J, Wejksza K, Zdzisińska B, Kandefer-Szerszeń M. Betulinic acid decreases expression of bcl-2 and cyclin D1, inhibits proliferation, migration and induces apoptosis in cancer cells.. Naunyn Schmiedebergs Arch Pharmacol 2006 Oct;374(1):11-20.
- Mullauer FB, van Bloois L, Daalhuisen JB, Ten Brink MS, Storm G, Medema JP, Schiffelers RM, Kessler JH. Betulinic acid delivered in liposomes reduces growth of human lung and colon cancers in mice without causing systemic toxicity.. Anticancer Drugs 2011 Mar;22(3):223-33.
- Chintharlapalli S, Papineni S, Lei P, Pathi S, Safe S. Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors.. BMC Cancer 2011 Aug 24;11:371.
- Zhao J, Li R, Pawlak A, Henklewska M, Sysak A, Wen L, Yi JE, Obmińska-Mrukowicz B. Antitumor Activity of Betulinic Acid and Betulin in Canine Cancer Cell Lines.. In Vivo 2018 Sep-Oct;32(5):1081-1088.
- Wang W, Wang Y, Liu M, Zhang Y, Yang T, Li D, Huang Y, Li Q, Bai G, Shi L. Betulinic acid induces apoptosis and suppresses metastasis in hepatocellular carcinoma cell lines in vitro and in vivo.. J Cell Mol Med 2019 Jan;23(1):586-595.
- Fulda S, Friesen C, Los M, Scaffidi C, Mier W, Benedict M, Nuñez G, Krammer PH, Peter ME, Debatin KM. Betulinic acid triggers CD95 (APO-1/Fas)- and p53-independent apoptosis via activation of caspases in neuroectodermal tumors.. Cancer Res 1997 Nov 1;57(21):4956-64.
- Fulda S, Scaffidi C, Susin SA, Krammer PH, Kroemer G, Peter ME, Debatin KM. Activation of mitochondria and release of mitochondrial apoptogenic factors by betulinic acid.. J Biol Chem 1998 Dec 18;273(51):33942-8.
- Mullauer FB, Kessler JH, Medema JP. Betulinic acid induces cytochrome c release and apoptosis in a Bax/Bak-independent, permeability transition pore dependent fashion.. Apoptosis 2009 Feb;14(2):191-202.
- Raghuvar Gopal DV, Narkar AA, Badrinath Y, Mishra KP, Joshi DS. Protection of Ewing's sarcoma family tumor (ESFT) cell line SK-N-MC from betulinic acid induced apoptosis by alpha-DL-tocopherol.. Toxicol Lett 2004 Nov 2;153(2):201-12.
- Tiwari R, Puthli A, Balakrishnan S, Sapra BK, Mishra KP. Betulinic acid-induced cytotoxicity in human breast tumor cell lines MCF-7 and T47D and its modification by tocopherol.. Cancer Invest 2014 Oct;32(8):402-8.
- Tan Y, Yu R, Pezzuto JM. Betulinic acid-induced programmed cell death in human melanoma cells involves mitogen-activated protein kinase activation.. Clin Cancer Res 2003 Jul;9(7):2866-75.
- Karna E, Szoka L, Palka JA. Betulinic acid inhibits the expression of hypoxia-inducible factor 1alpha and vascular endothelial growth factor in human endometrial adenocarcinoma cells.. Mol Cell Biochem 2010 Jul;340(1-2):15-20.
- Ren W, Qin L, Xu Y, Cheng N. Inhibition of betulinic acid to growth and angiogenesis of human colorectal cancer cell in nude mice.. Chinese-German J Clin Oncol 2010;9:153–157.
- Potze L, Mullauer FB, Colak S, Kessler JH, Medema JP. Betulinic acid-induced mitochondria-dependent cell death is counterbalanced by an autophagic salvage response.. Cell Death Dis 2014 Apr 10;5(4):e1169.
- Zuco V, Supino R, Righetti SC, Cleris L, Marchesi E, Gambacorti-Passerini C, Formelli F. Selective cytotoxicity of betulinic acid on tumor cell lines, but not on normal cells.. Cancer Lett 2002 Jan 10;175(1):17-25.
- Selzer E, Pimentel E, Wacheck V, Schlegel W, Pehamberger H, Jansen B, Kodym R. Effects of betulinic acid alone and in combination with irradiation in human melanoma cells.. J Invest Dermatol 2000 May;114(5):935-40.
- Potze L, Di Franco S, Grandela C, Pras-Raves ML, Picavet DI, van Veen HA, van Lenthe H, Mullauer FB, van der Wel NN, Luyf A, van Kampen AH, Kemp S, Everts V, Kessler JH, Vaz FM, Medema JP. Betulinic acid induces a novel cell death pathway that depends on cardiolipin modification.. Oncogene 2016 Jan 28;35(4):427-37.
- Liebscher G, Vanchangiri K, Mueller T, Feige K, Cavalleri JM, Paschke R. 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 2016 Feb 25;246:20-9.
- McFadyean J. Equine melanomatosis.. J Comp Pathol Ther 1933;46:186–IN8.
- Valentine BA. Equine melanocytic tumors: a retrospective study of 53 horses (1988 to 1991).. J Vet Intern Med 1995 Sep-Oct;9(5):291-7.
- Moore JS, Shaw C, Shaw E, Buechner-Maxwell V, Scarratt WK, Crisman M. Melanoma in horses: current perspectives.. Equine Vet Educ 2013;25:144–151.
- Rosengren Pielberg G, Golovko A, Sundström E, Curik I, Lennartsson J, Seltenhammer MH, Druml T, Binns M, Fitzsimmons C, Lindgren G, Sandberg K, Baumung R, Vetterlein M, Strömberg S, Grabherr M, Wade C, Lindblad-Toh K, Pontén F, Heldin CH, Sölkner J, Andersson L. A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse.. Nat Genet 2008 Aug;40(8):1004-9.
- Sundström E, Komisarczuk AZ, Jiang L, Golovko A, Navratilova P, Rinkwitz S, Becker TS, Andersson L. Identification of a melanocyte-specific, microphthalmia-associated transcription factor-dependent regulatory element in the intronic duplication causing hair greying and melanoma in horses.. Pigment Cell Melanoma Res 2012 Jan;25(1):28-36.
- Seltenhammer MH, Simhofer H, Scherzer S, Zechner R, Curik I, Sölkner J, Brandt SM, Jansen B, Pehamberger H, Eisenmenger E. Equine melanoma in a population of 296 grey Lipizzaner horses.. Equine Vet J 2003 Mar;35(2):153-7.
- Pilsworth RC, Knottenbelt DK. Melanoma.. Equine Vet Educ 2006;18:228–230.
- MacGillivray KC, Sweeney RW, Del Piero F. Metastatic melanoma in horses.. J Vet Intern Med 2002 Jul-Aug;16(4):452-6.
- Sundberg JP, Burnstein T, Page EH, Kirkham WW, Robinson FR. Neoplasms of Equidae.. J Am Vet Med Assoc 1977 Jan 15;170(2):150-2.
- Scott D. Neoplastic diseases.. In: Pedersen D, editor. Large Anim. Dermatology. Philadelphia: W.B. Saunders Company; 1988. pp. 448–452.
- Patterson-Kane JC, Sanchez LC, Uhl EW, Edens LM. Disseminated metastatic intramedullary melanoma in an aged grey horse.. J Comp Pathol 2001 Aug-Oct;125(2-3):204-7.
- Borges IL, Lima TDS, Vale RG, Augusto P, Borges C, Batista S. Metastatic cutaneous melanoma in equine: anatomopathological aspects.. Artig Científico Med Veterinária Metastatic 2017;11:32–38.
- Metcalfe LV, O'Brien PJ, Papakonstantinou S, Cahalan SD, McAllister H, Duggan VE. Malignant melanoma in a grey horse: case presentation and review of equine melanoma treatment options.. Ir Vet J 2013 Nov 6;66(1):22.
- Strauss RA, Allbaugh RA, Haynes J, Ben‐Shlomo G. Primary corneal malignant melanoma in a horse.. Equine Veterinary Education 2017;31(8):403–409.
- Müller J, Feige K, Wunderlin P, Hödl A, Meli ML, Seltenhammer M, Grest P, Nicolson L, Schelling C, Heinzerling LM. Double-blind placebo-controlled study with interleukin-18 and interleukin-12-encoding plasmid DNA shows antitumor effect in metastatic melanoma in gray horses.. J Immunother 2011 Jan;34(1):58-64.
- Rowe EL, Sullins KE. Excision as treatment of dermal melanomatosis in horses: 11 cases (1994-2000).. J Am Vet Med Assoc 2004 Jul 1;225(1):94-6.
- Groom LM, Sullins KE. Surgical excision of large melanocytic tumours in grey horses: 38 cases (2001–2013). Equine Vet Educ 2018;30:438–443.
- Théon AP, Wilson WD, Magdesian KG, Pusterla N, Snyder JR, Galuppo LD. Long-term outcome associated with intratumoral chemotherapy with cisplatin for cutaneous tumors in equidae: 573 cases (1995-2004).. J Am Vet Med Assoc 2007 May 15;230(10):1506-13.
- Hewes CA, Sullins KE. Use of cisplatin-containing biodegradable beads for treatment of cutaneous neoplasia in equidae: 59 cases (2000-2004).. J Am Vet Med Assoc 2006 Nov 15;229(10):1617-22.
- Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.. J Immunol Methods 1983 Dec 16;65(1-2):55-63.
- Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, Warren JT, Bokesch H, Kenney S, Boyd MR. New colorimetric cytotoxicity assay for anticancer-drug screening.. J Natl Cancer Inst 1990 Jul 4;82(13):1107-12.
- Fulda S, Kroemer G. Targeting mitochondrial apoptosis by betulinic acid in human cancers.. Drug Discov Today 2009 Sep;14(17-18):885-90.
- Kommera H, Kaluđerović GN, Kalbitz J, Paschke R. Lupane triterpenoids--betulin and betulinic acid derivatives induce apoptosis in tumor cells.. Invest New Drugs 2011 Apr;29(2):266-72.
- Kommera H, Kaluderović GN, Dittrich S, Kalbitz J, Dräger B, Mueller T, Paschke R. Carbamate derivatives of betulinic acid and betulin with selective cytotoxic activity.. Bioorg Med Chem Lett 2010 Jun 1;20(11):3409-12.
- Jiang L, Chen FX, Zang ST, Yang QF. Betulinic acid prevents high glucose‑induced expression of extracellular matrix protein in cardiac fibroblasts by inhibiting the TGF‑β1/Smad signaling pathway.. Mol Med Rep 2017 Nov;16(5):6320-6325.
- Ali-Seyed M, Jantan I, Vijayaraghavan K, Bukhari SN. Betulinic Acid: Recent Advances in Chemical Modifications, Effective Delivery, and Molecular Mechanisms of a Promising Anticancer Therapy.. Chem Biol Drug Des 2016 Apr;87(4):517-36.
- Smith SH, Goldschmidt MH, McManus PM. A comparative review of melanocytic neoplasms.. Vet Pathol 2002 Nov;39(6):651-78.
- Seltenhammer MH, Heere-Ress E, Brandt S, Druml T, Jansen B, Pehamberger H, Niebauer GW. Comparative histopathology of grey-horse-melanoma and human malignant melanoma.. Pigment Cell Res 2004 Dec;17(6):674-81.
- Mills PC, Cross SE. Regional differences in the in vitro penetration of hydrocortisone through equine skin.. J Vet Pharmacol Ther 2006 Feb;29(1):25-30.
- Luís A, Ruela M, Perissinato AG, Esselin M, Lino DS. Evaluation of skin absorption of drugs from topical and transdermal formulations.. Brazilian J Pharm Sci 2016;52:527–544.
- Dehelean CA, Feflea S, Ganta S, Amiji M. Anti-angiogenic effects of betulinic acid administered in nanoemulsion formulation using chorioallantoic membrane assay.. J Biomed Nanotechnol 2011 Apr;7(2):317-24.
- Emmett MS, Dewing D, Pritchard-Jones RO. Angiogenesis and melanoma - from basic science to clinical trials.. Am J Cancer Res 2011;1(7):852-68.
- Huyke C, Reuter J, Rödig M, Kersten A, Laszczyk M, Scheffler A, Nashan D, Schempp C. Treatment of actinic keratoses with a novel betulin-based oleogel. A prospective, randomized, comparative pilot study.. J Dtsch Dermatol Ges 2009 Feb;7(2):128-33.
- Mählmann K. Minimalistic immunologically defined gene expression T helper cell 1 (MIDGE-Th1®) vectors coding for Interleukin 12 and −18 in combination with the transfection agent SAINT-18 have systemic antitumoral effects on equine melanomas. vol. 3: Cuvillier Verlag Göttingen; 2012.
- Werner A, Braun M, Kietzmann M. Isolation and cultivation of canine corneal cells for in vitro studies on the anti-inflammatory effects of dexamethasone.. Vet Ophthalmol 2008 Mar-Apr;11(2):67-74.
- Gillies RJ, Didier N, Denton M. Determination of cell number in monolayer cultures.. Anal Biochem 1986 Nov 15;159(1):109-13.
- Team RDC, R development Core Team R. R: A Language and Environment for Statistical Computing.. 2008.
- Wood SN. Fast stable restricted maximum likelihood and marginal likelihood estimation of semiparametric generalized linear models.. J R Stat Soc Ser B Stat Methodol 2011;73:3–36.
- Hothorn T, Bretz F, Westfall P. Simultaneous inference in general parametric models.. Biom J 2008 Jun;50(3):346-63.
- Wickham H. Ggplot: elegant graphics for data analysis.. J Stat Softw 2010;35:1–3.
Citations
This article has been cited 14 times.- Pimenta J, Prada J, Cotovio M. Equine Melanocytic Tumors: A Narrative Review. Animals (Basel) 2023 Jan 10;13(2).
- Rednic R, Macasoi I, Pinzaru I, Dehelean CA, Tomescu MC, Susan M, Feier H. Pharmaco-Toxicological Assessment of the Combined Cytotoxic Effects of Digoxin and Betulinic Acid in Melanoma Cells. Life (Basel) 2022 Nov 11;12(11).
- Tuli HS, Sak K, Gupta DS, Kaur G, Aggarwal D, Chaturvedi Parashar N, Choudhary R, Yerer MB, Kaur J, Kumar M, Garg VK, Sethi G. Anti-Inflammatory and Anticancer Properties of Birch Bark-Derived Betulin: Recent Developments. Plants (Basel) 2021 Dec 3;10(12).
- 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).
- 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.
- Koltai T, Fliegel L. Anoikis: To Die or Not to Die?. Int J Mol Sci 2026 Jan 6;27(2).
- Cristea AM, Smeu A, Cîmpeanu IA, Iftode A, Liga S, Tchiakpe-Antal DS, Vlad D, Dehelean CA, Iliescu D. Biological Effects of Rosaceae Species in Skin Disorders-An Up-To-Date Overview. Plants (Basel) 2025 May 24;14(11).
- Cardinaux EM, Oltmanns H, Beineke A, Meißner J, Geburek F. Pharmacological alternatives to oxytetracycline as potential treatment of flexural limb deformities in foals: a preliminary in vitro cell viability and proliferation study. Sci Rep 2025 May 6;15(1):15762.
- 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.
- 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.
- Njikam J, Joshi A, Njoya EM, Upadhyay K, Ngnameko CR, McGaw LJ, Devkar RV, Njayou FN, Moundipa PF. Bioactive Fractions Isolated from Harungana madagascariensis Lam. and Psorospermum aurantiacum Engl. Regulate Collagen and Melanin Biosynthesis Gene Expression in UVB-irradiated Cells with Additional Anti-inflammatory Potential. Curr Drug Res Rev 2025;17(1):113-125.
- Gao Y, Packeiser EM, Wendt S, Sekora A, Cavalleri JV, Pratscher B, Alammar M, Hühns M, Brenig B, Junghanss C, Nolte I, Murua Escobar H. Cross-Species Comparison of the Pan-RAF Inhibitor LY3009120's Anti-Tumor Effects in Equine, Canine, and Human Malignant Melanoma Cell Lines. Genes (Basel) 2024 Feb 3;15(2).
- Wang S, Zhang Y, Yang X, Wang K, Yang X, Zhang B, Zhang B, Bie Q. Betulinic acid arrests cell cycle at G2/M phase by up-regulating metallothionein 1G inhibiting proliferation of colon cancer cells. Heliyon 2024 Jan 15;10(1):e23833.
- Grudzińska M, Stachnik B, Galanty A, Sołtys A, Podolak I. Progress in Antimelanoma Research of Natural Triterpenoids and Their Derivatives: Mechanisms of Action, Bioavailability Enhancement and Structure Modifications. Molecules 2023 Nov 24;28(23).
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists