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Toxicol In Vitro. 2016 Dec;37:148-161. doi: 10.1016/j.tiv.2016.09.017. Epub 2016 Sep 19.

Selective anticancer activity of the novel thiobenzanilide 63T against human lung adenocarcinoma cells.

Author information

1
Department of Toxicology, Poznan University of Medical Sciences, Poznan, Poland.
2
Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, Poznan, Poland.
3
Department of Immunology, Chair of Clinical Immunology, Poznan University of Medical Sciences, Poznan, Poland.
4
Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Poland; Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, Poznan, Poland.
5
Department of Medicinal Chemistry, University of Vienna, Vienna, Austria.
6
Department of Clinical Pharmacy and Diagnostics, University of Vienna, Austria.
7
Department of Pharmacognosy, University of Vienna, Austria.
8
Department of Toxicology, Poznan University of Medical Sciences, Poznan, Poland. Electronic address: marek.murias@ump.edu.pl.

Abstract

Previously, it has been reported that molecules built on the benzanilide and thiobenzanilide scaffold are the promising groups of compounds with several biological activities including antifungal, antimycotic, antibacterial, spasmolytic, and anticancer ones. In this study the mechanism of action of one selected thiobenzanilide derivative N,N'-(1,2-phenylene)bis3,4,5-trifluorobenzothioamide (63T) with strongest cytotoxic activity has been investigated for the first time in human lung adenocarcinoma (A549) and normal lung derived fibroblast (CCD39Lu) in a cell culture model. The results demonstrated, that 63T can be considered a selective anticancer compound. Based on these results, several experiments including the analysis of cellular morphology, cell phase distribution, cytoplasmic histone-associated DNA fragmentation, apoptosis, necrosis, and autophagy detection were performed to understand better the mechanism underlying the anticancer activity. The data showed that 63T is a small molecule compound, which selectively induces cancer cell death in a caspase independent pathway; moreover, the autophagic dose-dependent processes may be involved in the mechanism of cell death.

KEYWORDS:

A549; Apoptosis; Autophagy; Benzanilide; CCD39Lu; Lung cancer

PMID:
27660182
DOI:
10.1016/j.tiv.2016.09.017
[Indexed for MEDLINE]

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