betulin is a potent anti-tumor agent that is enhanced by cholesterol桦木醇是一种有效的抗肿瘤剂增强的胆固醇.pdfVIP

Betulin Is a Potent Anti-Tumor Agent that Is Enhanced by Cholesterol 1 1,2 1 Franziska B. Mullauer , Jan H. Kessler , Jan Paul Medema * 1 Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Experimental and Molecular Medicine, Academic Medical Center (AMC), Amsterdam, The Netherlands, 2 Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Leiden, The Netherlands Abstract Betulinic Acid (BetA) and its derivatives have been extensively studied in the past for their anti-tumor effects, but relatively little is known about its precursor Betulin (BE). We found that BE induces apoptosis utilizing a similar mechanism as BetA and is prevented by cyclosporin A (CsA). BE induces cell death more rapidly as compared to BetA, but to achieve similar amounts of cell death a considerably higher concentration of BE is needed. Interestingly, we observed that cholesterol sensitized cells to BE-induced apoptosis, while there was no effect of cholesterol when combined with BetA. Despite the significantly enhanced cytotoxicity, the mode of cell death was not changed as CsA completely abrogated cell death. These results indicate that BE has potent anti-tumor activity especially in combination with cholesterol. Citation: Mullauer FB, Kessler JH, Medema JP (2009) Betulin Is a Potent Anti-Tumor Agent that Is Enhanced by Cholesterol. PLoS ONE 4(4): e1. doi:10.1371/ journal.pone.0005361 Editor: Mikhail V. Blagosklonny, Ordway Research Institute, United States of America Received February 12, 2009; Accepted March 23, 2009; Published April 28, 2009 Copyright: 2009 Mullauer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits