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Anti-Cancer Agents in Medicinal Chemistry

Author(s): Szymon Kowalski, Aleksandra Tesmar, Artur Sikorski and Iwona Inkielewicz-Stępniak*

DOI: 10.2174/1871520620666200624145217

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Oxidovanadium(IV) Complex Disrupts Mitochondrial Membrane Potential and Induces Apoptosis in Pancreatic Cancer Cells

Page: [71 - 83] Pages: 13

  • * (Excluding Mailing and Handling)

Abstract

Background: At the present time, there is a growing interest in metal-based anticancer agents. Metal complexes exhibit many valuable clinical properties, however, due to toxicity, only a few clinically useful complexes have been discovered. It has been demonstrated that synthetic vanadium complexes exhibit many biological activities, including anti-cancer properties, however, cellular and molecular mechanisms still are not fully understood.

Objective: This investigation examined the potential effects of three newly synthesized oxidovanadium(IV) complexes with 2-amino-3-hydroxypyridine against pancreatic cancer cells.

Methods: We measured cytotoxicity by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, antiproliferative activity by bromodeoxyuridine assay and necrosis as well as late apoptosis by lactate dehydrogenase assay. Reactive oxygen species generation, apoptosis and mitochondrial membrane potential were determined by a flow cytometry technique. Cell morphology was evaluated by using a transmission electron microscope.

Results: The results showed that oxidovanadium(IV) complexes were cytotoxic on pancreatic cancer cells (PANC-1 and MIA PaCa2) over the concentration range of 12.5-200μM, following 48h incubation. Additionally, the cellular mechanism of cytotoxic activity of [2-NH2-3-OH(py)H]4[V2O2(pmida)2]·6H2O (V3) complex was dependent on ROS generation, induction apoptosis with simultaneous disruption of mitochondrial membrane potential.

Conclusion: We have proven that oxidovanadium (IV) complexes show therapeutic potential in pancreatic cancer therapy. The results of our research will help to understand the cellular mechanisms of the cytotoxic activity of the vanadium complexes and will allow a more effective design structure of new vanadium-based compounds in the future.

Keywords: Pancreatic cancer, vanadium complex, oxidative stress, mitochondrial membrane potential, apoptosis, 2-amino-3- hydroxypyridine.

Graphical Abstract

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