Betulin Is a Potent Anti-Tumor Agent that Is Enhanced by Cholesterol
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TLDR
BE induces apoptosis utilizing a similar mechanism as BetA and is prevented by cyclosporin A (CsA), which indicates that BE has potent anti-tumor activity especially in combination with cholesterol.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.read more
Citations
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References
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Depletion of membrane cholesterol causes ligand-independent activation of Fas and apoptosis.
TL;DR: It is proposed that in some cell types exclusion of Fas from lipid rafts leads to the spontaneous, ligand-independent activation of this death receptor, a mechanism that can potentially be utilized in anticancer therapy.
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A Preliminary Pharmacokinetic Study of Betulin, the Main Pentacyclic Triterpene from Extract of Outer Bark of Birch (Betulae alba cortex)
TL;DR: Preliminary pharmacokinetics of betulin and results of a subchronic toxicity study of TE in rats and dogs show triterpene extract from birch bark is safe, its betulin is bioavailable and in addition to published triterpenes biological activities TE provides high potential for further pharmaceutical and pharmacological research.
Journal ArticleDOI
Betulinic acid induces cytochrome c release and apoptosis in a Bax/Bak-independent, permeability transition pore dependent fashion
TL;DR: It is shown that BetA-induced apoptosis critically depends on the release of cytochrome c from the mitochondria and formation of the apoptosome, and helps to explain the remarkable broad efficacy of BetA against tumor cells of different origin and its effect in tumor cells that are resistant to other chemotherapeutic agents.
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Preparation of amino acid conjugates of betulinic acid with activity against human melanoma.
TL;DR: It is demonstrated that amino acid conjugates of betulinic acid can produce potentially important derivatives, which may be developed as antitumor agents, and improved water solubility as well as selective cytotoxicity.
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Synthesis of phthalates of betulinic acid and betulin with cytotoxic activity.
TL;DR: It was discovered that hemiphthalic esters had better cytotoxicity than starting compounds as betulinic acid or quite inactive betulin.
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