Physico-chemical comparison of betulinic acid, betulin and birch bark extract andin vitroinvestigation of their cytotoxic effects towards skin epidermoid carcinoma (A431), breast carcinoma (MCF7) and cervix adenocarcinoma (HeLa) cell lines

Abstract

Betulin and betulinic acid are pentacyclic triterpenes present in the bark of the birch tree and other vegetal sources. Quantitatively, in birch bark betulin is more significant than betulinic acid; therefore, birch can be a large and feasible source of raw material for betulin extraction. Betulin can be used as extracted or, after chemical modification, as a starting compound for its acid, betulinic acid, with both substances possessing various interesting pharmacological properties. The purpose of this study is to analyse the betulin and betulinic acid content of a birch tree bark extract, as well as its cytotoxic activity. The extraction was done using a Soxhlet extractor and chloroform/dichlormethane/methanol (1 : 1 : 1) as solvent. The betulin and betulinic acid content of the extract was estimated using standards of pure betulin and betulinic acid, by thermal analysis as opposed to pure substance (thermogravimetric and differential thermal analysis). The extract and the main compounds were also analysed by NMR. The results indicated a high amount of betulin in the final extract (up to 50%), and an important quantity of betulinic acid: over 3%. The cytotoxic activity indicated a high proliferation inhibition for the birch tree extract but was still comparable with betulinic acid and betulin.

Study of the betulin enriched birch bark extracts effects on human carcinoma cells and ear inflammation

“…The present report continues the work previously presented [12] by our team, falling in a project which focuses on finding new antitumor natural sources like birch bark; in the same time our present report brings important new research data. We improved in a unique manner the extraction procedure of betulin and betulinic acid from birch bark, by obtaining a higher amount of active compound (over 90%) than previous studies.…”

Induction of cell cycle arrest and apoptosis by betulinic acid-rich fraction from Dillenia suffruticosa root in MCF-7 cells involved p53/p21 and mitochondrial signalling pathway

“…Quantification of betulinic acid (BA) in DCM-DS was performed by Alliance high performance liquid chromatography (HPLC) (Waters, USA) according to previously published method with some modifications Şoica et al, 2012). The chromatography was carried out using a reversed-phase C18 Chromolith column (5 mm, 50 mm  2 mm) (Merck, Darmstadt, Germany).…”

Simultaneous and Dose Dependent Melanoma Cytotoxic and Immune Stimulatory Activity of Betulin

“…Specifically hints towards the TLR-mediated PAMP/DAMP-dependent IL-12 induction had been gathered from publications [11–13]. Additionally, all three candidates are published to have potential antiproliferative or proapoptotic activity in different cancer cell types [14–16]. This finally led to the selection of these three prototypical "mild" but comparable cytostatic compounds with at the same time, concomitantly highly differential effects on third signal generation by DCs.…”

“…The precursor of BA, betulin, has been less well studied than its carboxylic form. Betulin exhibited inhibitory activity against A431, HeLa and MCF-7 cell lines and showed anti-angiogenic activity, which was determined by a clear reduction of blood vessel formation [16]. It was also active in skin cancerogenesis, as reported in a model of chemically induced cutaneous carcinoma [25].…”