Planta Med 2010; 76 - P610
DOI: 10.1055/s-0030-1264908

Betulin in formulation with ramified gamma type cyclodextrin targeting tumour cells and angiogenesis

S Feflea 1, C Peev 1, C Soica 1, S Ciurlea 1, C Dehelean 1
  • 1University of Medicine and Pharmacy „Victor Babes“ Timisoara, Pharmacognosy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania

Betulin is a pentacyclic triterpenic compound, found in important quantities in the bark of birch trees, widespread in northern latitude areas. It is known to possess multiple biological activities, including anti-inflammatory, antiviral and anticancer effects [1] and acting as an antimelanoma agent by binding to the melanocortin receptor subtype 1 (also expressed by endothelial cells) [2], which represented an indication to a possible angiogenic – modulator activity. This study aimed to evaluate the effect of betulin on tumor cell lines – A431 (skin epidemoid carcinoma), HeLa (cervix crcinoma), and MCF7 (breast adenocarcinoma) – using the MTT assay, and on the angiogenesis process by performing the in ovo chick chorioallantoic membrane (CAM) assay [3]. The formulation with cyclodextrin (Oktakis (2,6di-O-pentyl)-gamma cyclodextrin) was prepared applying a specific technique: dissolution with an organic solvent (chloroform) and polysorbate 20, stirring and evaporation under vacuum. Different dilutions of a 0,01mg/ml betulin stock solution showed on tumor cells antiproliferative properties. Inhibition rate ranged for A431 between 72–80%, for MCF7 between 35–55% and for HeLa between 75–82%. We applied nanoformulations of cyclodextrin complexed with betulin onto the rapid growing CAM. Histological and morphometric evaluation of treated specimens showed modifications both of the CAM epithelium, mesenchyme and of the capillaries, indicating an indirect inhibition of the angiogenic process. The in vitro and in vivo results suggest that betulin can represent a possible antitumor as well as an antimetastatic compound.

Acknowledgements: This work was supported by CNCSIS-UEFISCSU, project number PN II- IDEI code 1257/2007.

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2. Muceniece R. et al. (2007) Cell biochem funct. 25(5): 591–596.

3. Ribatti D. et al. (2006) Nat protoc. 1(1): 85–91.