New oxidovanadium(IV) coordination complex containing 2-methylnitrilotriacetate ligands induces cell cycle arrest and autophagy in human pancreatic ductal adenocarcinoma cell lines

Szymon Kowalski , Dariusz Wyrzykowski , Stanisław Hac , Michał Rychłowski , Marek Witold Radomski , Iwona Inkielewicz-Stepniak


Pancreatic cancer is characterized by one of the lowest five-year survival rates. In search for new treatments, some studies explored several metal complexes as potential anticancer drugs. Therefore, we investigated three newly synthesized oxidovanadium(IV) complexes with 2-methylnitrilotriacetate (bcma3−), N-(2-carbamoylethyl)iminodiacetate (ceida3−) and N-(phosphonomethyl)-iminodiacetate (pmida4−) ligands as potential anticancer compounds using pancreatic cancer cell lines. We measured: Cytotoxicity using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), neutral red (NR) and lactate dehydrogenase (LDH) assay; antiproliferative activity by bromodeoxyuridine BrdU assay; reactive oxygen species (ROS) generation and cell cycle analysis by flow cytometry; protein level by Western blot and cellular morphology by confocal laser scanning microscopy. The results showed that these oxidovanadium(IV) complexes were cytotoxic on pancreatic cancer cells (PANC-1 and MIA PaCa2), but not on non-tumor human immortalized pancreas duct epithelial cells (hTERT-HPNE) over the concentration range of 10–25 μM, following 48 h incubation. Furthermore, molecular mechanisms of cytotoxicity of [4-NH2-2-Me(Q)H][VO(bcma)(H2O)]2H2O (T1) were dependent on antiproliterative activity, increased ROS generation, cell cycle arrest in G2/M phase with simultaneous triggering of the p53/p21 pathway, binucleation, and induction of autophagy. Our study indicates that oxidovanadium(IV) coordination complexes containing 2-methylnitrilotriacetate ligand are good candidates for preclinical development of novel anticancer drugs targeting pancreatic cancer.
Author Szymon Kowalski
Szymon Kowalski,,
, Dariusz Wyrzykowski (FCh/DGICh/PBChN)
Dariusz Wyrzykowski,,
- Pracownia Biologicznej Chemii Nieorganicznej
, Stanisław Hac
Stanisław Hac,,
, Michał Rychłowski (IFB/IB/LVMB)
Michał Rychłowski,,
- Laboratory of Virus Molecular Biology
, Marek Witold Radomski
Marek Witold Radomski,,
, Iwona Inkielewicz-Stepniak
Iwona Inkielewicz-Stepniak,,
Journal seriesInternational Journal of Molecular Sciences, ISSN 1422-0067, (N/A 140 pkt)
Issue year2019
Publication size in sheets0.95
Article number261
Keywords in Englishvanadium complex, pancreatic cancer, autophagy, mitotic catastrophe, cell cycle arrest
ASJC Classification2700 General Medicine; 1312 Molecular Biology; 1503 Catalysis; 1604 Inorganic Chemistry; 1605 Organic Chemistry; 1606 Physical and Theoretical Chemistry; 1607 Spectroscopy; 1706 Computer Science Applications
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)140
Score sourcejournalList
ScoreMinisterial score = 140.0, 03-02-2020, ArticleFromJournal
Publication indicators WoS Citations = 1.000; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 1.224; WoS Impact Factor: 2018 = 4.183 (2) - 2018=4.331 (5)
Citation count*6 (2020-04-21)
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