The antitumor activity of a lead thioxanthone is associated with alterations in cholesterol localization

Raquel T. Lima, Diana Sousa, Ana Sara Gomes, Nuno Mendes, Rune Matthiesen, Madalena Pedro, Franklim Marques, Madalena M. Pinto, Emília Sousa, M. Helena Vasconcelos

Research output: Contribution to journalArticle

4 Citations (Scopus)
6 Downloads (Pure)

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.

Original languageEnglish
Article number3301
JournalMolecules
Volume23
Issue number12
DOIs
Publication statusPublished - 12 Dec 2018

Keywords

  • Antitumor activity
  • Cholesterol localization
  • Non-small cell lung cancer
  • Rags
  • Thioxanthones
  • Tumor xenografts

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