Betulin is a potent anti-tumor agent that is enhanced by cholesterol.
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.
Mullauer
Franziska B
FB
Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Experimental and Molecular Medicine, Academic Medical Center (AMC), Amsterdam, The Netherlands.
Kessler
Jan H
JH
Medema
Jan Paul
JP
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D002784:Cholesterol / Q000008:administration & dosage*; D016572:Cyclosporine / Q000494:pharmacology; D004357:Drug Synergism; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D015870:Gene Expression; D019254:Genes, bcl-2; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D018345:Mice, Knockout; D053978:Pentacyclic Triterpenes; D017382:Reactive Oxygen Species / Q000378:metabolism; D014315:Triterpenes / Q000008:administration & dosage*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000172:deficiency / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000172:deficiency / Q000235:genetics; D000094062:Betulinic Acid
D000972:Antineoplastic Agents, Phytogenic; C494773:Bak1 protein, mouse; C494827:Bax protein, mouse; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D053978:Pentacyclic Triterpenes; D017382:Reactive Oxygen Species; D014315:Triterpenes; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; C002503:betulin; D016572:Cyclosporine; D002784:Cholesterol; D000094062:Betulinic Acid