{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T01:01:04Z","timestamp":1773882064491,"version":"3.50.1"},"reference-count":71,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2018,12,12]],"date-time":"2018-12-12T00:00:00Z","timestamp":1544572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PEst-C\/SAU\/LA0003\/2013; POCI-01-0145-FEDER-007274; UID\/Multi\/04423\/2013"],"award-info":[{"award-number":["PEst-C\/SAU\/LA0003\/2013; POCI-01-0145-FEDER-007274; UID\/Multi\/04423\/2013"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The search for novel anticancer small molecules and strategies remains a challenge. Our previous studies have identified TXA1 (1-{[2-(diethylamino)ethyl]amino}-4-propoxy-9H- thioxanthen-9-one) as a hit compound, with in vitro antitumor potential by modulating autophagy and apoptosis in human tumor cell lines. In the present study, the mechanism of action and antitumor potential of the soluble salt of this molecule (TXA1.HCl) was further investigated using in vitro and mouse xenograft tumor models of NSCLC. Our results showed that TXA1.HCl affected steroid biosynthesis, increased RagD expression, and caused abnormal cellular cholesterol localization. In addition, TXA1.HCl treatment presented no toxicity to nude mice and significantly reduced the growth of human NSCLC cells xenografts in mice. Overall, this work provides new insights into the mechanism of action of TXA1, which may be relevant for the development of anticancer therapeutic strategies, which target cholesterol transport.<\/jats:p>","DOI":"10.3390\/molecules23123301","type":"journal-article","created":{"date-parts":[[2018,12,12]],"date-time":"2018-12-12T10:54:26Z","timestamp":1544612066000},"page":"3301","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The Antitumor Activity of a Lead Thioxanthone is Associated with Alterations in Cholesterol Localization"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5838-9659","authenticated-orcid":false,"given":"Raquel T.","family":"Lima","sequence":"first","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Cancer Drug Resistance Group\u2014IPATIMUP\u2014Institute of Molecular Pathology and Immunology of the University of Porto; Rua J\u00falio Amaral de Carvalho, 45, 4200-135 Porto, Portugal"},{"name":"Department of Pathology, Faculty of Medicine of the University of Porto, Alameda Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"given":"Diana","family":"Sousa","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Cancer Drug Resistance Group\u2014IPATIMUP\u2014Institute of Molecular Pathology and Immunology of the University of Porto; Rua J\u00falio Amaral de Carvalho, 45, 4200-135 Porto, Portugal"},{"name":"Laboratory of Microbiology, Department of Biological Sciences, FFUP-Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9378-6043","authenticated-orcid":false,"given":"Ana Sara","family":"Gomes","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Department of Biological Sciences, FFUP-Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"UCIBIO, REQUIMTE, Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0570-2277","authenticated-orcid":false,"given":"Nuno","family":"Mendes","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"HEMS-Histology and Electron Microscopy-i3S, Rua J\u00falio Amaral de Carvalho, 45, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6353-2616","authenticated-orcid":false,"given":"Rune","family":"Matthiesen","sequence":"additional","affiliation":[{"name":"Computational and Experimental Biology Group, The Chronic Diseases Research Center (CEDOC), Nova Medical School, Faculdade de Ciencias Medicas Universidade Nova De Lisboa, Rua C\u00e2mara Pestana 61150-082 Lisboa, Portugal"}]},{"given":"Madalena","family":"Pedro","sequence":"additional","affiliation":[{"name":"CESPU, Instituto de Investiga\u00e7\u00e3o e Forma\u00e7\u00e3o Avan\u00e7ada em Ci\u00eancias e Tecnologias da Sa\u00fade, IUCS-Instituto Universit\u00e1rio de Ci\u00eancias da Sa\u00fade, Rua Central de Gandra 1317, 4585-116 Gandra, Portugal"}]},{"given":"Franklim","family":"Marques","sequence":"additional","affiliation":[{"name":"UCIBIO, REQUIMTE, Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4676-1409","authenticated-orcid":false,"given":"Madalena M.","family":"Pinto","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, FFUP-Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"CIIMAR\/CIMAR\u2014Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental, Universidade do Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Avenida General Norton de Matos, S\/N, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5397-4672","authenticated-orcid":false,"given":"Em\u00edlia","family":"Sousa","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, FFUP-Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"CIIMAR\/CIMAR\u2014Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental, Universidade do Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Avenida General Norton de Matos, S\/N, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7801-4643","authenticated-orcid":false,"given":"M. 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