Betulin Elicits Anti-Cancer Effects in Tumour Primary Cultures and Cell Lines In Vitro. Basic & Clinical Pharmacology & Toxicology.
Abstract:  Betulin is a pentacyclic triterpene found in many plant species, among others, in white birch bark. The aim of the study was in vitro characterization of the anticancer activity of betulin in a range of human tumour cell lines (neuroblastoma, rhabdomyosarcoma-medulloblastoma, glioma, thyroid, breast, lung and colon carcinoma, leukaemia and multiple myeloma), and in primary tumour cultures isolated from patients (ovarian carcinoma, cervical carcinoma and glioblastoma multiforme). In this study, we demonstrated a remarkable anti-proliferative effect of betulin in all tested tumour cell cultures. Neuroblastoma (SK-N-AS) and colon carcinoma (HT-29) were the most sensitive to the anti-proliferative effect of betulin. Furthermore, betulin altered tumour cells morphology, decreased their motility and induced apoptotic cell death. These findings demonstrate the anti-cancer potential of betulin and suggest that they may be applied as an adjunctive measure in cancer treatment
Rzeski W, Stepulak A, Szymanski M et al. Volume 105, Issue 6, pages 425–432, December 2009. DOI: 10.1111/j.1742-7843.2009.00471.x

Anti-Cancer Effect of Betulin on a Human Lung Cancer Cell Line: A Pharmacoproteomic Approach Using 2 D SDS PAGE Coupled with Nano-HPLC Tandem Mass Spectrometry.
Betulin is a representative compound of Betula platyphylla, a tree species belonging to the Betulaceae family. In this investigation, we revealed that betulin showed anticancer activity on human lung cancer A549 cells by inducing apoptosis and changes in protein expression profiles were observed. Upon flow cytometry analysis, the surface of betulin-treated cells was found to be annexin-V positive and propidium iodide (PI) negative, which indicated that the cells were apoptotic. In order to identify the molecular players involved in betulin-induced apoptosis, cellular proteins were applied to two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (2 D SDS PAGE) for differential proteomic analysis. As a result, four downregulated proteins and three upregulated proteins were identified by nano-HPLC MS/MS. The four downregulated proteins were poly(rC)-binding protein 1, isoform 1 of 3-hydroxyacyl-CoA dehydrogenase type 2, heat shock protein 90-alpha 2, and enoyl-CoA hydratase; the three upregulated proteins were aconitate hydratase, malate dehydrogenase, and splicing factor arginine/serine-rich 1. These differentially expressed proteins explained the cytotoxicity of betulin against human lung cancer A549 cells, and the proteomic approach was thus shown to be a potential tool for understanding the pharmacological activities of pharmacophores.
Pyo JS, Roh SH, Kim DK, Lee JG, Lee YY, Hong SS, Kwon SW, & Park JH. Planta Med 2009; 75(2): 127-131. DOI: 10.1055/s-0028-1088366

Inhibition Effect of Betulin on Oesophageal Cancer EC109 Cell Line
BACKGROUND & AIM: Betulin is an important triterpene. We investigated the antitumor activity of betulin, extracted from the bark of silver birch (Betula platyphylla Suk).
MATERIAL AND METHODS: Betulin was isolated from dry powder of the bark of silver birch (Betula platyphylla Suk) by using ethanol circumfluence, decompress concentration and methanol-chloroform recrystallization. The inhibition rate on EC109 cell growth was detected by MTT (Methylthiazoletetrazolium) method, after the oesophageal cancer EC109 cells have been treated for 48h with different doses of betulin.
RESULTS: With the increasing doses of betulin, the inhibition rate of EC109 cell growth was increased, and their morphological characteristics were changed significamtly. The inhibition rate showed dose-dependent relation.
CONCLUSION: Betulin had potent inhibiting effects on EC109 cells growth in vitro.
Cai W-j, Ma Y-q, Qi Y-m et al. Carcinogenesis,Teratogenesis & Mutagenesis. 2006; 18(1) Pp.016-8. CN:44-1063/R   

Esters of betulin and betulinic acid with amino acids have improved water solubility and are selectively cytotoxic toward cancer cells
Betulin and betulinic acid are naturally occurring pentacyclic triterpenes showing cytotoxicity towards a number of cancer cell lines. Unfortunately they are practically insoluble in aqueous media and therefore their overall absorption index is not satisfactory. We have modified structures of both compounds by simple transformation to mono- and disubstituted esters of l-amino acids. This allowed us to achieve better water solubility without loss of the observed earlier anticancer properties. Comet assay on various cancer cell lines demonstrate that these compounds act via an apoptotic mechanism.
Drag-Zalesinska M et al. Bioorganic & Medicinal Chemistry Letters. Volume 19, Issue 16, 15 August 2009, Pages 4814-4817. doi:10.1016/j.bmcl.2009.06.046

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