{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T12:37:47Z","timestamp":1764333467589,"version":"build-2065373602"},"reference-count":75,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["COVID\/BD\/151978\/2021","SFRH\/BD\/133207\/2017","UID\/BIA\/04050\/2020","UID\/QUI\/0686\/2020","PTDC\/QUIQIN\/28662\/2017"],"award-info":[{"award-number":["COVID\/BD\/151978\/2021","SFRH\/BD\/133207\/2017","UID\/BIA\/04050\/2020","UID\/QUI\/0686\/2020","PTDC\/QUIQIN\/28662\/2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Specific cancer therapy remains a problem to be solved. Breast and colorectal cancer are among the cancers with the highest prevalence and mortality rates. Although there are some therapeutic options, there are still few effective agents for those cancers, which constitutes a clinical problem that requires further research efforts. Lysosomes play an important role in cancer cells\u2019 survival, and targeting lysosomes has gained increased interest. In recent years, our team has been synthetizing and testing novel benzo[a]phenoxazine derivatives, as they have been shown to possess potent pharmacological activities. Here, we investigated the anticancer activity of three of the most potent derivatives from our library, C9, A36, and A42, on colorectal- and breast-cancer-derived cell lines, and compared this with the effect on non-neoplastic cell lines. We observed that the three compounds were selective for the cancer cells, namely the RKO colorectal cancer cell line and the MCF7 breast cancer cell line. In both models, the compounds reduced cell proliferation, cell survival, and cell migration, accumulated on the lysosome, and induced cell death accompanied by lysosomal membrane permeabilization (LMP), increasing the intracellular pH and ROS accumulation. Our results demonstrated that these compounds specifically target lysosomes from cancer cells, making them promising candidates as LMP inducers for cancer therapy.<\/jats:p>","DOI":"10.3390\/cells13161385","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T06:07:35Z","timestamp":1724134055000},"page":"1385","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Anticancer Activity of Benzo[a]phenoxazine Compounds Promoting Lysosomal Dysfunction"],"prefix":"10.3390","volume":"13","author":[{"given":"Jo\u00e3o Carlos Canossa","family":"Ferreira","sequence":"first","affiliation":[{"name":"Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"IBS-Institute of Science and Innovation for Bio-Sustainability, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"Centre of Chemistry (CQUM), Department of Chemistry, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2048-1190","authenticated-orcid":false,"given":"M. Sameiro T.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Centre of Chemistry (CQUM), Department of Chemistry, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7302-0630","authenticated-orcid":false,"given":"Ana","family":"Preto","sequence":"additional","affiliation":[{"name":"Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"IBS-Institute of Science and Innovation for Bio-Sustainability, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9424-4150","authenticated-orcid":false,"given":"Maria Jo\u00e3o","family":"Sousa","sequence":"additional","affiliation":[{"name":"Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"IBS-Institute of Science and Innovation for Bio-Sustainability, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1002\/cncr.33587","article-title":"The ever-increasing importance of cancer as a leading cause of premature death worldwide","volume":"127","author":"Bray","year":"2021","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA. 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