{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T11:32:07Z","timestamp":1784719927097,"version":"3.55.0"},"reference-count":34,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T00:00:00Z","timestamp":1713744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ACIMAGO","award":["07\/07"],"award-info":[{"award-number":["07\/07"]}]},{"name":"ACIMAGO","award":["UIDB\/04539\/2020 (10.54499\/UIDB\/04539\/2020)"],"award-info":[{"award-number":["UIDB\/04539\/2020 (10.54499\/UIDB\/04539\/2020)"]}]},{"name":"ACIMAGO","award":["UIDP\/04539\/2020 (10.54499\/UIDP\/04539\/2020)"],"award-info":[{"award-number":["UIDP\/04539\/2020 (10.54499\/UIDP\/04539\/2020)"]}]},{"name":"ACIMAGO","award":["LA\/P\/0058\/2020 (10.54499\/LA\/P\/0058\/2020)"],"award-info":[{"award-number":["LA\/P\/0058\/2020 (10.54499\/LA\/P\/0058\/2020)"]}]},{"name":"Foundation for Science and Technology (FCT), Portugal","award":["07\/07"],"award-info":[{"award-number":["07\/07"]}]},{"name":"Foundation for Science and Technology (FCT), Portugal","award":["UIDB\/04539\/2020 (10.54499\/UIDB\/04539\/2020)"],"award-info":[{"award-number":["UIDB\/04539\/2020 (10.54499\/UIDB\/04539\/2020)"]}]},{"name":"Foundation for Science and Technology (FCT), Portugal","award":["UIDP\/04539\/2020 (10.54499\/UIDP\/04539\/2020)"],"award-info":[{"award-number":["UIDP\/04539\/2020 (10.54499\/UIDP\/04539\/2020)"]}]},{"name":"Foundation for Science and Technology (FCT), Portugal","award":["LA\/P\/0058\/2020 (10.54499\/LA\/P\/0058\/2020)"],"award-info":[{"award-number":["LA\/P\/0058\/2020 (10.54499\/LA\/P\/0058\/2020)"]}]},{"name":"Associated Laboratory funding","award":["07\/07"],"award-info":[{"award-number":["07\/07"]}]},{"name":"Associated Laboratory funding","award":["UIDB\/04539\/2020 (10.54499\/UIDB\/04539\/2020)"],"award-info":[{"award-number":["UIDB\/04539\/2020 (10.54499\/UIDB\/04539\/2020)"]}]},{"name":"Associated Laboratory funding","award":["UIDP\/04539\/2020 (10.54499\/UIDP\/04539\/2020)"],"award-info":[{"award-number":["UIDP\/04539\/2020 (10.54499\/UIDP\/04539\/2020)"]}]},{"name":"Associated Laboratory funding","award":["LA\/P\/0058\/2020 (10.54499\/LA\/P\/0058\/2020)"],"award-info":[{"award-number":["LA\/P\/0058\/2020 (10.54499\/LA\/P\/0058\/2020)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2019s therapeutic potential in hematological malignancies, with daily dosing emerging as a strategy to minimize adverse effects.<\/jats:p>","DOI":"10.3390\/ijms25084554","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T07:44:09Z","timestamp":1713771849000},"page":"4554","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Batimastat Induces Cytotoxic and Cytostatic Effects in In Vitro Models of Hematological Tumors"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2599-6433","authenticated-orcid":false,"given":"Raquel","family":"Alves","sequence":"first","affiliation":[{"name":"Laboratory of Oncobiology and Hematology (LOH), University Clinics of Hematology and Oncology, Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Group of Environmental Genetics of Oncobiology (CIMAGO), FMUC, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), 3004-504 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Pires","sequence":"additional","affiliation":[{"name":"Laboratory of Oncobiology and Hematology (LOH), University Clinics of Hematology and Oncology, Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"HistologiX, BioCity, Innovation, Pennyfoot St., Nottingham NG1 1GF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0755-8077","authenticated-orcid":false,"given":"Joana","family":"Jorge","sequence":"additional","affiliation":[{"name":"Laboratory of Oncobiology and Hematology (LOH), University Clinics of Hematology and Oncology, Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Group of Environmental Genetics of Oncobiology (CIMAGO), FMUC, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), 3004-504 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Bal\u00e7a-Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Oncobiology and Hematology (LOH), University Clinics of Hematology and Oncology, Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"NOVA Medical School, New University of Lisbon, 1150-090 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1470-4802","authenticated-orcid":false,"given":"Ana Cristina","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Laboratory of Oncobiology and Hematology (LOH), University Clinics of Hematology and Oncology, Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Group of Environmental Genetics of Oncobiology (CIMAGO), FMUC, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), 3004-504 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4142-4841","authenticated-orcid":false,"given":"Ana Bela","family":"Sarmento-Ribeiro","sequence":"additional","affiliation":[{"name":"Laboratory of Oncobiology and Hematology (LOH), University Clinics of Hematology and Oncology, Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Group of Environmental Genetics of Oncobiology (CIMAGO), FMUC, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), 3004-504 Coimbra, Portugal"},{"name":"Hematology Service, Centro Hospitalar Universit\u00e1rio de Coimbra, Unidade Local de Sa\u00fade de Coimbra, 3000-061 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1038\/s41375-019-0674-7","article-title":"Bone marrow niche-derived extracellular matrix-degrading enzymes influence the progression of B-cell acute lymphoblastic leukemia","volume":"34","author":"Verma","year":"2020","journal-title":"Leukemia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1016\/j.it.2019.09.006","article-title":"Metalloproteases: On the Watch in the Hematopoietic Niche","volume":"40","author":"Saw","year":"2019","journal-title":"Trends Immunol."},{"key":"ref_3","first-page":"519","article-title":"Matrix 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