Planta Med 2014; 80 - P1L8
DOI: 10.1055/s-0034-1394666

The evaluation of betulin and betulinic acid on B164A5 melanoma cells in chorioallantoic membrane assay

S Avram 1, D Gheorgheosu 2, AM Cimpean 3, C Danciu 1, IZ Pavel 1, SI Avram 4, C Soica 5, C Peev 1, C Dehelean 2, M Raica 3
  • 1Department of Pharmacognosy, Faculty of Pharmacy, University of Medicine and Pharmacy “Victor Babes“, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania
  • 2Department of Toxicology, Faculty of Pharmacy, University of Medicine and Pharmacy “Victor Babes“, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania
  • 3Department of Histology, Faculty of Medicine, University of Medicine and Pharmacy “Victor Babes“, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania
  • 4Department of Computational Chemistry, Institute of Chemistry of Romanian Academy Timisoara, Mihai Viteazul Avenue 24, Timisoara 300223, Romania
  • 5Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy “Victor Babes“, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania

Cutaneous melanoma is one of the most violent forms of skin cancer due to high malignant potential. Advances in molecular therapeutic approaches are still confronted with resistance and very low survival [1]. More efficient, with low toxicity, natural agents are studied for their chemopreventive and anti-tumor potential. Here, we investigated two pentacyclic triterpenes, betulin (Bet) and betulinic acid (BA), compounds found in birch tree bark, known for anticancer, antiviral, anti-inflammatory and antiangiogenic effects [2, 3]. Both compounds in different formulations were evaluated on a B164A5 melanoma assay using the chick embryo chorioallantoic membrane (CAM). By performing stereomicroscopy and histologic evaluation we found that Bet inhibited the growth of tumor cells in the primary site stronger than BA and induced impairments to the pigmentation and adhesion characteristics of melanoma cells. BA had limited to a higher extent the invasion from secondary formed tumor sites, showing a lower vascular density. Both compounds were well tolerated, inducing no modification to the normal CAM. Capillaries inside tumor areas were observed, but angiogenesis was not exacerbated. The two compounds did not inhibit the formation of secondary tumors. Acting differently, Bet and BA limited the growth of B164A5 melanoma cells and the formation of new capillaries both at primary and secondary sites.

Acknowledgements: Research was supported by an Internal grant at UMFT Victor Babes, PII-C2-TC-2014, CAMMelRasNa, obtained by Avram Stefana.

Keywords: Betulin, betulinic acid, melanoma, B164A5, angiogenesis, chorioallantoic membrane

References:

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[2.] Laszczyk MN. Pentacyclic triterpenes of the lupane, oleanane and ursane group as tools in cancer therapy. Planta Med 2009; 75: 1549 – 1560.

[3] Dehelean CA, Feflea S, Gheorgheosu D, Ganta S, Cimpean AM, Muntean D, Amiji MM. Anti-angiogenic and anti-cancer evaluation of betulin nanoemulsion in chicken chorioallantoic membrane and skin carcinoma in Balb/c mice. J Biomed Nanotechnol 2013; 9: 577 – 589.