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Synergistic AML Cell Death Induction by Marine Cytotoxin (+)-1(R), 6(S), 1'(R), 6'(S), 11(R), 17(S)-Fistularin-3 and Bcl-2 Inhibitor Venetoclax ArchiMer
Florean, Cristina; Kim, Kyung Rok; Schnekenburger, Michael; Kim, Hyun-jung; Moriou, Celine; Debitus, Cecile; Dicato, Mario; Al-mourabit, Ali; Han, Byung Woo; Diederich, Marc.
Treatment of acute myeloid leukemia (AML) patients is still hindered by resistance and relapse, resulting in an overall poor survival rate. Recently, combining specific B-cell lymphoma (Bcl)-2 inhibitors with compounds downregulating myeloid cell leukemia (Mcl)-1 has been proposed as a new effective strategy to eradicate resistant AML cells. We show here that 1(R), 6(S), 1'(R), 6'(S), 11(R), 17(S)-fistularin-3, a bromotyrosine compound of the fistularin family, isolated from the marine sponge Suberea clavata, synergizes with Bcl-2 inhibitor ABT-199 to efficiently kill Mcl-1/Bcl-2-positive AML cell lines, associated with Mcl-1 downregulation and endoplasmic reticulum stress induction. The absolute configuration of carbons 11 and 17 of the fistularin-3...
Tipo: Text Palavras-chave: Acute myeloid leukemia; ABT-199; Mcl-1; Bromotyrosine; (+)-11(R); 17(S)-fistularin-3; Configuration; Anticancer drug combination.
Ano: 2018 URL:
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