2026-04-14T03:57:42Zhttps://recercat.cat/oai/request

oai:recercat.cat:2117/3591882026-01-30T07:18:36Zcom_2072_1033col_2072_452950

00925njm 22002777a 4500 dc Reis-Silva, Catarina Sofia Mateus author Branco, Paola Cristina author Lima, Keli author Silva, Fabiana Lima author Moreno, Paulo Roberto Hrihorowitsch author Guallar, Victor author Costa Lotufo, Leticia Veras author Machado Neto, João Agostinho author 2021 Acute myeloid leukemia (AML) belongs to a group of hematological cancer whose relapse cases are often associated with chemoresistance that impairs treatment success and contributes to a poor outcome. For this reason, there is an urgent need for the development of new therapeutic strategies. Herein, we explore the combination of venetoclax, a BCL2 inhibitor, and embelin, an XIAP inhibitor, in the AML cell lines. Combinatory treatment of venetoclax and embelin potentiated cytotoxic effects of these drugs, demonstrating that both in combination present lower IC50 values than single treatment of either venetoclax or embelin alone in both cell lines analyzed. The combinatory treatment further increased the apoptosis-inducing properties of both compounds. Computer simulations suggest that embelin binds to both BIR2 and BIR3 domains of XIAP, reinforcing this inhibitory apoptosis protein as an embelin target. Although all AML cell lines presented similar basal levels of XIAP, the combinatory treatment effectively inhibited XIAP expression in OCI-AML3 cells. In conclusion, the inhibition of both apoptosis inhibitory players, BCL2 and XIAP, by venetoclax and embelin, respectively, potentiated their cytotoxic effects in AML cell lines. The authors want to express their acknowledgements to Prof. Dr. Eduardo Magalhaes Rego (University of Sao Paulo, Ribeirao Preto, Brazil) for providing leukemia cell lines. We are also grateful for the embelin HPLC analysis by Prof. Marcelo Jose Pena Ferreira (IB-USP). This work was supported by Fundaçao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Brazil, under processes 2019/23864-7, 2018/ 06522-2, 2017/09022–8, and 2015/17177–6. This study was financed in part by the Coordenaçao de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001. Postprint (author's final draft) Àrees temàtiques de la UPC::Informàtica::Aplicacions de la informàtica::Bioinformàtica Acute myeloid leukemia Cell lines Acute myeloid leukemia Embelin Venetoclax Apoptosis Leucèmia Embelin potentiates venetoclax-induced apoptosis in acute myeloid leukemia cells