ArticleBiological procedures online2026
Ethacrynic Oxadiazole 6u Induces Apoptosis by Targeting mTOR/c-Flip Axis and Noxa in Lymphoma Cells.
Article in Biological procedures online, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundEvasion of apoptosis is a major cause of therapy failure in lymphoma. We studied a covalent compound 6u with an α, β-saturated carbonyl group derived from the diuretic drug ethacrynic acid to induce apoptosis of lymphoma cells by targeting antiapoptotic proteins.
resultsWe found that 6u induces apoptosis in 4 lymphoma cell lines, Daudi, Romas, Jeko-1 and Jurkat, accompanied by down-regulation of c-Flip and Mcl-1, as well as upregulation of Noxa. The down-regulation of Mcl-1 relies on Noxa induction and that the down-regulation of c-Flip is mediated by inhibiting protein synthesis pathway through covalent binding to mTOR complexes. Overexpression of c-Flip and silencing Noxa attenuate 6u-induced apoptosis. 6u modified with the saturated carbonyl structure loses the mTOR inhibition and apoptosis induction abilities. 6u exhibits potent anti-lymphoma effects in mantle cell lymphoma Jeko-1 xenografts without causing toxicity.
conclusion6u functions as an apoptosis inducer through the α, β-saturated carbonyl group to decrease c-Flip and to induce Noxa. 6u represents a new type of covalent agent for targeting lymphoma by inducing apoptosis.
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