Oxidovanadium(IV) Complex Disrupts Mitochondrial Membrane Potential and Induces Apoptosis in Pancreatic Cancer Cells.
Aminopyridines
/ chemistry
Antineoplastic Agents
/ chemistry
Apoptosis
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Coordination Complexes
/ chemistry
Drug Screening Assays, Antitumor
Humans
Ligands
Membrane Potential, Mitochondrial
/ drug effects
Oxidative Stress
/ drug effects
Pancreas
/ cytology
Pancreatic Neoplasms
/ drug therapy
Structure-Activity Relationship
Tetrazolium Salts
/ chemistry
Thiazoles
/ chemistry
Vanadium
/ chemistry
Pancreatic Neoplasms
2-amino-3-
hydroxypyridine
Pancreatic cancer
apoptosis
mitochondrial membrane potential
oxidative stress
vanadium complex
Journal
Anti-cancer agents in medicinal chemistry
ISSN: 1875-5992
Titre abrégé: Anticancer Agents Med Chem
Pays: Netherlands
ID NLM: 101265649
Informations de publication
Date de publication:
2021
2021
Historique:
received:
11
01
2020
revised:
14
04
2020
accepted:
24
04
2020
pubmed:
25
6
2020
medline:
16
6
2021
entrez:
25
6
2020
Statut:
ppublish
Résumé
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. This investigation examined the potential effects of three newly synthesized oxidovanadium(IV) complexes with 2-amino-3-hydroxypyridine against pancreatic cancer cells. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 32579508
pii: ACAMC-EPUB-107611
doi: 10.2174/1871520620666200624145217
doi:
Substances chimiques
Aminopyridines
0
Antineoplastic Agents
0
Coordination Complexes
0
Ligands
0
Tetrazolium Salts
0
Thiazoles
0
Vanadium
00J9J9XKDE
thiazolyl blue
EUY85H477I
2-amino-3-hydroxypyridine
P8740PEW4B
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
71-83Subventions
Organisme : Medical University of Gdansk
ID : MN-010319/08/259, ST-46
Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.