title: Selective anticancer activity of the novel thiobenzanilide 63T against human lung adenocarcinoma cells.
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.
authors.affiliation: Department of Toxicology, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kucinska
authors.affiliation: Department of Toxicology, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Piotrowska-Kempisty
authors.affiliation: Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Lisiak
authors.affiliation: Department of Immunology, Chair of Clinical Immunology, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Kaczmarek
authors.affiliation: Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Poland; Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, Poznan, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Dams-Kozlowska
authors.affiliation: Department of Medicinal Chemistry, University of Vienna, Vienna, Austria.
authors.forename: Walter H
authors.initials: WH
authors.lastname: Granig
authors.affiliation: Department of Clinical Pharmacy and Diagnostics, University of Vienna, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Höferl
authors.affiliation: Department of Clinical Pharmacy and Diagnostics, University of Vienna, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Jäger
authors.affiliation: Department of Pharmacognosy, University of Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Zehl
authors.affiliation: Department of Toxicology, Poznan University of Medical Sciences, Poznan, Poland. Electronic address: marek.murias@ump.edu.pl.
authors.forename: Marek
authors.initials: M
authors.lastname: Murias
authors.affiliation: Department of Medicinal Chemistry, University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Erker
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001555:Benzene Derivatives / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D006801:Humans; D008175:Lung Neoplasms; D009336:Necrosis / Q000139:chemically induced; D013854:Thioamides / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001555:Benzene Derivatives; C557928:N,N'-(1,2-phenylene)bis(3,4,5-trifluorobenzothioamide); D013854:Thioamides; D020169:Caspases
keywords: A549; Apoptosis; Autophagy; Benzanilide; CCD39Lu; Lung cancer