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    Betulenic Acid and Lonidamide Betulenic acid is a pentacyclic triterpene proposed as an anticancer drug. When only small amounts of electrophilic metabolites are formed, they are detoxified by glutathione, and direct toxicity does not occur.

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  • Were the first to demonstrate this in a viagra a prescription drug murine fibrosarcoma cell. The effect of GSH depletion in sensitizing to the lethal actions of TNFα has received Mechanisms of Cell Death 71 considerable attention. However, it is unclear whether the increase in Bax or other effects of decreased GSH mediate the increased susceptibility. They showed that depletion of mitochondrial GSH markedly enhanced the TNFαinduced oxidative stress and killing, whereas lesser depletion of mainly cytosol GSH was ineffective (19). It has been proposed that this involves the activation of acidic sphingomyelinase and the release of ceramide and its products, which then act on mitochondria to block electron transport at the complex III–ubiquinone cycle leading to auto-oxidation of O 1 from the buildup of electrons (28).

    Intracellular signaling following the binding of TNFα to TNF-R1 leads to increased reactive oxygen metabolite production in mitochondria. This effect correlated with GSH depletion-induced upregulation of p23 (presumably via oxidative stress) and consequent upregulation of Bax.

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