Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/115122
Title: Batimastat Induces Cytotoxic and Cytostatic Effects in In Vitro Models of Hematological Tumors
Authors: Alves, Raquel 
Pires, Ana 
Jorge, Joana 
Balça-Silva, Joana 
Gonçalves, Ana Cristina 
Sarmento-Ribeiro, Ana Bela 
Keywords: acute leukemia; apoptosis; batimastat (BB-94); matrix metalloproteinase; multiple myeloma; myelodysplasia
Issue Date: 22-Apr-2024
Publisher: MDPI
Project: info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/LA/P/0058/2020/PT 
UIDB/04539/2020 
info:eu-repo/grantAgreement/UIDP/04539/2020 
metadata.degois.publication.title: International Journal of Molecular Sciences
metadata.degois.publication.volume: 25
metadata.degois.publication.issue: 8
Abstract: The role of metalloproteinases (MMPs) in hematological malignancies, like acute myeloid leukemia (AML), myelodysplastic neoplasms (MDS), and multiple myeloma (MM), is well-documented, and these pathologies remain with poor outcomes despite treatment advancements. In this study, we investigated the effects of batimastat (BB-94), an MMP inhibitor (MMPi), in single-administration and daily administration schemes in AML, MDS, and MM cell lines. We used four hematologic neoplasia cell lines: the HL-60 and NB-4 cells as AML models, the F36-P cells as an MDS model, and the H929 cells as a model of MM. We also tested batimastat toxicity in a normal human lymphocyte cell line (IMC cells). BB-94 decreases cell viability and density in a dose-, time-, administration-scheme-, and cell-line-dependent manner, with the AML cells displaying higher responses. The efficacy in inducing apoptosis and cell cycle arrests is dependent on the cell line (higher effects in AML cells), especially with lower daily doses, which may mitigate treatment toxicity. Furthermore, BB-94 activated apoptosis via caspases and ERK1/2 pathways. These findings highlight batimastat's therapeutic potential in hematological malignancies, with daily dosing emerging as a strategy to minimize adverse effects.
URI: https://hdl.handle.net/10316/115122
ISSN: 1422-0067
DOI: 10.3390/ijms25084554
Rights: openAccess
Appears in Collections:I&D CIBB - Artigos em Revistas Internacionais
I&D ICBR - Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais

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