Selective cytotoxicity of vanadium complexes on human pancreatic ductal adenocarcinoma cell line by inducing necroptosis, apoptosis and mitotic catastrophe process

Abstract

// Szymon Kowalski 1 , Stanisław Hać 2 , Dariusz Wyrzykowski 3 , Agata Zauszkiewicz-Pawlak 4 and Iwona Inkielewicz-Stępniak 1 1 Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland 2 Department of General, Endocrine and Transplantation Surgery, Medical University of Gdansk, Gdansk, Poland 3 Faculty of Chemistry, University of Gdansk, Gdansk, Poland 4 Department of Histology, Medical University of Gdansk, Gdansk, Poland Correspondence to: Iwona Inkielewicz-Stepniak, email: iinkiel@gumed.edu.pl Keywords: vanadium complexes, pancreatic cancer, necroptosis, mitotic catastrophe, autophagy Received: February 17, 2017     Accepted: May 22, 2017     Published: July 22, 2017 ABSTRACT The pancreatic cancer is the fourth leading cause of cancer-related death and characterized by one of the lowest five-year survival rate. The current therapeutic options are demonstrating minimal effectiveness, therefore studies on new potential anticancer compounds, with non-significant side effects are highly desirable. Recently, it was demonstrated that vanadium compounds, in particular organic derivatives, exhibit anticancer properties against different type of tumor as well as favorable biodistribution from a pancreatic cancer treatment perspective. In this research, we showed selective cytotoxic effect of vanadium complexes, containing phenanthroline and quinoline as an organic ligands, against human pancreatic ductal adenocarcinoma cell line (PANC-1), compared to non-tumor human immortalized pancreas duct epithelial cells (hTERT-HPNE). Results exhibited that vanadium complexes inhibited autophagy process in selective cytotoxic concentration as well as caused the cell cycle arrest in G2/M phase associated with mitotic catastrophe and increased level of reactive oxygen species (ROS). Moreover, in higher concentration, vanadium derivatives induced a mix type of cell death in PANC-1 cells, including apoptotic and necroptotic process. Our investigation emphasizes the anticancer potential of vanadium complexes by indicating their selective cytotoxic activity, through different process posed by alternative type of cell deaths to apoptosis-resistant cancer cells. Further studies supporting the therapeutic potential of vanadium in pancreatic cancer treatment is highly recommended.