Embelin potentiates venetoclax-induced apoptosis i... - BV FAPESP
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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Embelin potentiates venetoclax-induced apoptosis in acute myeloid leukemia cells

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Author(s):
Mateus Reis-Silva, Catarina Sofia [1] ; Branco, Paola Cristina [1] ; Lima, Keli [1, 2] ; Silva, Fabiana Lima [3] ; Hrihorowitsch Moreno, Paulo Roberto [3] ; Guallar, Victor [4, 5] ; Costa-Lotufo, Leticia Veras [1] ; Machado-Neto, Joao Agostinho [1]
Total Authors: 8
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Av Prof Lineu Prestes 1524, BR-05508900 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Fac Med, Dept Hematol, Lab Med Invest Pathogenesis & Targeted Therapy On, Sao Paulo - Brazil
[3] Univ Sao Paulo, Inst Chem, Sao Paulo - Brazil
[4] Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona - Spain
[5] Barcelona Supercomp Ctr BSC, Barcelona - Spain
Total Affiliations: 5
Document type: Journal article
Source: TOXICOLOGY IN VITRO; v. 76, OCT 2021.
Web of Science Citations: 0
Abstract

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. (AU)

FAPESP's process: 17/09022-8 - Inhibitory Apoptosis Proteins (IAPs) as therapeutic targets in melanoma: studies with prodiginines in vemurafenibe-resistant cells
Grantee:Paola Cristina Branco
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 19/23864-7 - Comprehensive analysis of genomic data for identification and validation of novel therapeutic targets involved in cellular cytoskeleton regulation in acute Leukemia
Grantee:João Agostinho Machado Neto
Support Opportunities: Regular Research Grants
FAPESP's process: 15/17177-6 - Integrative approach on the sustainable prospection of marine natural products: from diversity to anticancer compounds
Grantee:Leticia Veras Costa Lotufo
Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
FAPESP's process: 18/06522-2 - Use of bioaffinity chromatography in the prospecting of anticancer substances in marine actinomycetes: XIAP and STMN1 as pharmacological targets
Grantee:Catarina Sofia Mateus Reis e Silva
Support Opportunities: Scholarships in Brazil - Master