The Antitumor Activity of a Lead Thioxanthone is Associated with Alterations in Cholesterol Localization

• Tipo: Artigo em Revista Científica Internacional
• Data: 2018

Autores

Lima, RT (Autor) Outra; Sousa, D (Autor) Outra; Gomes, AS (Autor) Outra; Mendes, N (Autor) Outra; Matthiesen, R (Autor) Outra; Pedro, M (Autor) Outra; Franklim Marques (Autor) FFUP; Pinto, MM (Autor) Outra; Emilia Sousa (Autor) FFUP; Helena Vasconcelos, MH (Autor) FFUP

Revista

Título: Molecules

Nº de Série 9 Vol. 23 Nº 2288

Página Final: 3301

ISSN: 1420-3049

Editora: MDPI

Indexação

ISI Web of Knowledge - 8 Citações

Scopus - 9 Citações

Outras Informações

ID Authenticus: P-00Q-0Q4

DOI: 10.3390/molecules23123301

Abstract (EN): 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 19