{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T11:34:01Z","timestamp":1762083241055,"version":"build-2065373602"},"reference-count":68,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T00:00:00Z","timestamp":1672272000000},"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":["SFRH\/BD\/133207\/2017","COVID\/BD\/151978\/2021","UID\/BIA\/04050\/2020","UID\/QUI\/00686\/2016","UID\/QUI\/0686\/2020","PTDC\/QUIQIN\/28662\/2017","REDE\/1517\/RMN\/2005"],"award-info":[{"award-number":["SFRH\/BD\/133207\/2017","COVID\/BD\/151978\/2021","UID\/BIA\/04050\/2020","UID\/QUI\/00686\/2016","UID\/QUI\/0686\/2020","PTDC\/QUIQIN\/28662\/2017","REDE\/1517\/RMN\/2005"]}]},{"name":"National Program for Scientific Re-equipment","award":["SFRH\/BD\/133207\/2017","COVID\/BD\/151978\/2021","UID\/BIA\/04050\/2020","UID\/QUI\/00686\/2016","UID\/QUI\/0686\/2020","PTDC\/QUIQIN\/28662\/2017","REDE\/1517\/RMN\/2005"],"award-info":[{"award-number":["SFRH\/BD\/133207\/2017","COVID\/BD\/151978\/2021","UID\/BIA\/04050\/2020","UID\/QUI\/00686\/2016","UID\/QUI\/0686\/2020","PTDC\/QUIQIN\/28662\/2017","REDE\/1517\/RMN\/2005"]}]},{"name":"POCI 2010 (FEDER)","award":["SFRH\/BD\/133207\/2017","COVID\/BD\/151978\/2021","UID\/BIA\/04050\/2020","UID\/QUI\/00686\/2016","UID\/QUI\/0686\/2020","PTDC\/QUIQIN\/28662\/2017","REDE\/1517\/RMN\/2005"],"award-info":[{"award-number":["SFRH\/BD\/133207\/2017","COVID\/BD\/151978\/2021","UID\/BIA\/04050\/2020","UID\/QUI\/00686\/2016","UID\/QUI\/0686\/2020","PTDC\/QUIQIN\/28662\/2017","REDE\/1517\/RMN\/2005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Colorectal cancer (CRC) has been ranked as one of the cancer types with a higher incidence and one of the most mortal. There are limited therapies available for CRC, which urges the finding of intracellular targets and the discovery of new drugs for innovative therapeutic approaches. In addition to the limited number of effective anticancer agents approved for use in humans, CRC resistance and secondary effects stemming from classical chemotherapy remain a major clinical problem, reinforcing the need for the development of novel drugs. In the recent years, the phenoxazines derivatives, Nile Blue analogues, have been shown to possess anticancer activity, which has created interest in exploring the potential of these compounds as anticancer drugs. In this context, we have synthetized and evaluated the anticancer activity of different benzo[a]phenoxazine derivatives for CRC therapy. Our results revealed that one particular compound, BaP1, displayed promising anticancer activity against CRC cells. We found that BaP1 is selective for CRC cells and reduces cell proliferation, cell survival, and cell migration. We observed that the compound is associated with reactive oxygen species (ROS) generation, accumulates in the lysosomes, and leads to lysosomal membrane permeabilization, cytosolic acidification, and apoptotic cell death. In vivo results using a chicken embryo choriollantoic membrane (CAM) assay showed that BaP1 inhibits tumor growth, angiogenesis, and tumor proliferation. These observations highlight that BaP1 as a very interesting agent to disturb and counteract the important roles of lysosomes in cancer and suggests BaP1 as a promising candidate to be exploited as new anticancer lysosomal-targeted agent, which uses lysosome membrane permeabilization (LMP) as a therapeutic approach in CRC.<\/jats:p>","DOI":"10.3390\/ijms24010614","type":"journal-article","created":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T03:26:11Z","timestamp":1672370771000},"page":"614","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Targeting Lysosomes in Colorectal Cancer: Exploring the Anticancer Activity of a New Benzo[a]phenoxazine Derivative"],"prefix":"10.3390","volume":"24","author":[{"given":"Jo\u00e3o C. C.","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, Department of Chemistry, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"}]},{"given":"Sara","family":"Granja","sequence":"additional","affiliation":[{"name":"Department of Pathological, Cytological and Thanatological Anatomy, School of Health, Polytechnic Institute of Porto, 4200-072 Porto, Portugal"},{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4806-909 Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6663-6851","authenticated-orcid":false,"given":"Ana F.","family":"Almeida","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\/0000-0002-1770-4544","authenticated-orcid":false,"given":"F\u00e1tima","family":"Baltazar","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4806-909 Guimar\u00e3es, 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, 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":[[2022,12,29]]},"reference":[{"key":"ref_1","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 Cancer J. 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