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

Szymon Kowalski; Stanisław Hać; Dariusz Wyrzykowski; Agata Zauszkiewicz-Pawlak; Iwona Inkielewicz-Stępniak

doi:10.18632/oncotarget.19454

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Research Papers:

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

Szymon Kowalski, Stanisław Hać, Dariusz Wyrzykowski, Agata Zauszkiewicz-Pawlak and Iwona Inkielewicz-Stępniak _

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Oncotarget. 2017; 8:60324-60341. https://doi.org/10.18632/oncotarget.19454

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Abstract

Szymon Kowalski1, Stanisław Hać2, Dariusz Wyrzykowski3, Agata Zauszkiewicz-Pawlak4 and Iwona Inkielewicz-Stępniak1

1Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland

2Department of General, Endocrine and Transplantation Surgery, Medical University of Gdansk, Gdansk, Poland

3Faculty of Chemistry, University of Gdansk, Gdansk, Poland

4Department of Histology, Medical University of Gdansk, Gdansk, Poland

Correspondence to:

Iwona Inkielewicz-Stepniak, email: [email protected]

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.

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Research Papers:

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

Abstract