@article{00078eb30b064003b0cb2c8fd782faa6,
title = "The antitumor activity of a lead thioxanthone is associated with alterations in cholesterol localization",
abstract = "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.",
keywords = "Antitumor activity, Cholesterol localization, Non-small cell lung cancer, Rags, Thioxanthones, Tumor xenografts",
author = "Lima, {Raquel T.} and Diana Sousa and Gomes, {Ana Sara} and Nuno Mendes and Rune Matthiesen and Madalena Pedro and Franklim Marques and Pinto, {Madalena M.} and Em{\'i}lia Sousa and {Helena Vasconcelos}, M.",
note = "info:eu-repo/grantAgreement/FCT/COMPETE/132983/PT# info:eu-repo/grantAgreement/FCT/5876/147268/PT# IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT, the Portuguese Foundation for Science and Technology. This work is funded by FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE and National Funds through the FCT-Foundation for Science and Technology, under the projects {"}PEst-C/SAU/LA0003/2013{"}, ERDF, programme PT2020-Contributos para o reforco da capacidade do IPATIMUP enquanto actor do sistema regional de inovacao{"} and NORTE-07-0162-FEDER-000067-Reforco e consolidacao da capacidade infraestrutural do IPATIMUP para o sistema regional de inovacao{"}, both supported by Programa Operacional Regional do Norte (ON.2-O Novo Norte), through FEDER funds under the Quadro de Referencia Estrategico Nacional (QREN). This work was also financed by FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT-Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Inovacao in the framework of the project {"}Institute for Research and Innovation in Health Sciences{"} (POCI-01-0145-FEDER-007274). This work was also supported through national funds provided by FCT/MCTES-Foundation for Science and Technology from the Minister of Science, Technology and Higher Education (PIDDAC) and European Regional Development Fund (ERDF) through the COMPETE-Programa Operacional Factores de Competitividade (POFC) programme, under the Strategic Funding UID/Multi/04423/2013, in the framework of the programme PT2020. ",
year = "2018",
month = dec,
day = "12",
doi = "10.3390/molecules23123301",
language = "English",
volume = "23",
journal = "Molecules",
publisher = "MDPI - Multidisciplinary Digital Publishing Institute",
number = "12",
}
