Betulin Is a Potent Anti-Tumor Agent that Is Enhanced by Cholesterol

TLDR

Betulinic Acid and its derivatives have been studied for anti‑tumor effects, but little is known about its precursor Betulin. Betulin induces apoptosis via a mechanism similar to Betulinic Acid, is more rapid yet requires higher doses, and its cytotoxicity is markedly enhanced by cholesterol, though cyclosporin A fully blocks cell death.

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.