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

• Type: Article in International Scientific Journal
• Date: 2018

Authors

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

Journal

Title: Molecules

Serial No. 9 Vol. 23 No. 2288

Final page: 3301

ISSN: 1420-3049

Publisher: MDPI

Indexing

ISI Web of Knowledge - 8 Citations

Scopus - 9 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 19