Drug Res (Stuttg) 2020; 70(12): 545-551
DOI: 10.1055/a-1235-5565
Original Article

Induction of Cell Cycle Arrest in MKN45 Cells after Schiff Base Oxovanadium Complex Treatment Using Changes in Gene Expression of CdC25 and P53

Sara Mirjalili
1   Department of Biochemistry, Semnan University of Medical Sciences, Semnan, Iran
,
Maedeh Dejamfekr
1   Department of Biochemistry, Semnan University of Medical Sciences, Semnan, Iran
,
Abdolvahab Moshtaghian
2   Deputy of Research and Technology, Semnan University of Medical Sciences, Semnan, Iran
,
Mehdi Salehi
3   Department of Chemistry, College of Science, Semnan University, Semnan, Iran
,
Mahdi Behzad
3   Department of Chemistry, College of Science, Semnan University, Semnan, Iran
,
Ali Khaleghian
1   Department of Biochemistry, Semnan University of Medical Sciences, Semnan, Iran
› Author Affiliations
Funding: This research was supported by two grants (no: 934 and 1283) from Semnan university of medical sciences, Semnan, Iran.

Abstract

Compounds containing heavy metals such as vanadium, nickel, and cobalt may be useful for the treatment of various diseases. Multiple studies have been carried out on the anticancer effects of vanadium-contained compounds on different cell types. This study aimed to evaluate the role of schiff base oxovanadium complex ([N,N'-bis(3-methoxy-salicylidene)-1,2-phenylenediamine]Vanadium(IV) Oxide Complex) on cell cycle arrest and different cell cycle phases in MKN45 cell of gastric cancer. Schiff base oxovanadium complex was used to assessthe amount of cytotoxicity via cell viability test. PI color and flow cytometry technique were applied to evaluate the effects of vanadium synthetic compounds on cell cycle phases; subsequently, we analyzed the change rates of gene expression in P53, GADD45, and CDC25 genes, which are involved in cell division phases. The findings indicated that the vital activities of time-dependent and concentration-dependent MKN45 cells with schiff base oxovanadium complex were significantly reduced; therefore, this complex is able to inhibit the migration of cancer cells and metastatic activities in a time-dependent mode. Cell cycle arrest was obtained after 48 h of treatment in phase G2/M at 1 microgram/milliliter (μg/ml) concentration. This is probably attributed to the increased gene expression of P53 and GADD45 genes and reduced gene expression of CDC25 gene. Compounds containing such heavy metals as vanadium decrease the growth, proliferation, and migration of MKN45 cells. They arrest cell cycle in phase G2/M via changing the controllers of cell division phases activated due to DNA damage.



Publication History

Received: 03 March 2020

Accepted: 03 August 2020

Article published online:
04 September 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Hamid Bakhshi Aliabad, Soudeh Khanamani Falahati-pour, Hadis Ahmadirad et al. Vanadium complex: An appropriate candidate for killing hepatocellular carcinoma cancerous cells Biometals 2018
  • 2 Fang Jing, Yin Heng, Zheng Zhixiang. et al. The Molecular Mechanisms of Protective Role of Se on the G2/M Phase Arrest of Jejunum Caused by AFB1 Biol Trace Elem Res 2018; 181: 142-153
  • 3 Babaei Esmaeil, Ghojaie Manuchehr, Aas Zohre. et al. Evaluation of the Anti-cancer Effect of Nano-based Compound of Farnesiferol C on Cancerous Gastric Cell Lines 2015; 4 No. 2 141-146
  • 4 Eshaghi Malekshah R, Salehi M, Kubicki M. et al. New mononuclear copper(II) complexes from β-diketone and β-keto ester N-donor heterocyclic ligands: Structure, bioactivity, and molecular simulation studies. Journal of Coordination Chemistry 2018; 71 (07) pp 952-968
  • 5 Mazani M, Hadizadeh S, Najafzadeh N. et al. Anti-cancer Effects of Palladium Complexes on Gastric Cancer Cell Line (AGS). Journal of Guilan University of Medical Sciences 2014; 23: 72-79
  • 6 Aubrecht J, Narla RK, Ghosh P. et al. Molecular genotoxicity profiles of apoptosis-inducing vanadocene complexes. Toxicology and Applied Pharmacology 1999; 154: 228-235
  • 7 Faneca H, Figueiredo VA, Tomaz I. et al. Vanadium compounds as therapeutic agents: Some chemical and biochemical studies. Journal of Inorganic Biochemistry 2009; 103: 601-608
  • 8 Lampronti I, Bianchi N, Borgatti M. et al. Effects of vanadium complexes on cell growth of human leukemia cells and protein-DNA interactions. Oncology Reports 2005; 14: 9-15
  • 9 Molinuevo MS, Barrio DA, Cortizo AM. et al. Antitumoral properties of two new vanadyl (IV) complexes in osteoblasts in culture: Role of apoptosis and oxidative stress. Cancer Chemotherapy and Pharmacology 2004; 53: 163-172
  • 10 Michael B Ujiki, Xian-Zhong Ding, M Reza Salabat et al. Apigenin inhibits pancreatic cancer cell proliferation through G2/M cell cycle arrest Molecular Cancer 2006; 5: 76
  • 11 Kurt Engeland. Cell cycle arrest through indirect transcriptional repression by p53: I have a DREAM, Cell Death and Differentiation 2018; 25: 114-132
  • 12 Taheri O, Behzad M, Ghaffari A. et al. Synthesis, crystal structures and antibacterial studies of oxidovanadium(IV) complexes of salen-type Schiff base ligands derived from meso-1,2-diphenyl-1,2-ethylenediamine. Transition Metal Chemistry 2014; 39: 253-259
  • 13 Thompson HJ, Chasteen ND, Meeker LD. Dietary vanadyl(IV) sulfate inhibits chemically-induced mammary carcinogenesis. Carcinogenesis 1984; 5: 849-851
  • 14 Faneca H, Figueiredo VA, Tomaz I. et al. Vanadium compounds as therapeutic agents: Some chemical and biochemical studies. Journal of Inorganic Biochemistry 2009; 103: 601-608
  • 15 Lampronti I, Bianchi N, Borgatti M. et al. Effects of vanadium complexes on cell growth of human leukemia cells and protein-DNA interactions. Oncology Reports 2005; 14: 9-15
  • 16 Abbasi Z, Salehi M, Kubicki M. et al. New Ni(II) complexes involving symmetrical bidentate N,O-donor Schiff base ligands: synthesis at ambient temperature, crystal structures, electrochemical study, antioxidant and cytotoxic activities. Journal of Coordination Chemistry 2017; 70: 3132-3146
  • 17 Eshaghi Malekshah R, Salehi M, Kubicki M. et al. New mononuclear copper(II) complexes from β-diketone and β-keto ester N-donor heterocyclic ligands: Structure, bioactivity, and molecular simulation studies. Journal of Coordination Chemistry 2018; 71: 952-968
  • 18 Hassani S, Khaleghian A, Ahmadian S. et al. Redistribution of cell cycle by arsenic trioxide is associated with demethylation and expression changes of cell cycle related genes in acute promyelocytic leukemia cell line (NB4). Annals of Hematology 2018; 97 pp 83-93
  • 19 Khaleghian A, Ghaffari SH, Ahmadian S. et al. Metabolism of arsenic trioxide in acute promyelocytic leukemia cells. Journal of Cellular Biochemistry 2014; 115 pp 1729-1739
  • 20 Chien P-S, Mak O-T, Huang H-J. Induction of COX-2 protein expression by vanadate in A549 human lung carcinoma cell line through EGF receptor and p38 MAPK-mediated pathway. Biochemical and biophysical research communications 2006; 339: 562-568
  • 21 Abbasi Zeinab, Salehi Mehdi, Khaleghian Ali. et al. Co(III), V(IV) and Cu(II) complexes of bidentate N,O-donor Schiff base ligands: Characterization, anticancer activities and metal oxide nanoparticles preparation via solid state thermal decomposition, Applied Organometallic. Chemistry 2018; 32: e4542
  • 22 Meshkini Azadeh, Yazdanparast Razieh. Chemosensitization of human leukemia K562 cells to taxol by a Vanadium-salen complex. Experimental and Molecular Pathology 2010; 89: 334-342
  • 23 Koga A, Aoyagi K, Imaizumi T. et al. Comparison between the gastric cancer cell line MKN-45 and the high-potential peritoneal dissemination gastric cancer cell line MKN-45P. Kurume Med J 2011; 58: 73-79
  • 24 Ray RS, Ghosh B, Fau Rana A. et al. Suppression of cell proliferation, induction of apoptosis and cell cycle arrest: chemopreventive activity of vanadium in vivo and in vitro.
  • 25 Wu Y, Ma Y, Xu Z. et al. Sodium orthovanadate inhibits growth of human hepatocellular carcinoma cells in vitro and in an orthotopic model in vivo. Cancer letters 2014; 351: 108-116
  • 26 Nair RS, Kuriakose M, Somasundaram V. et al. The molecular response of vanadium complexes of nicotinoyl hydrazone in cervical cancers-A possible interference with HPV oncogenic markers. Life Sciences 2014; 116: 90-97
  • 27 Rozzo C, Sanna D, Garribba E. et al. Antitumoral effect of vanadium compounds in malignant melanoma cell lines. Journal of Inorganic Biochemistry 2017; 174: 14-24
  • 28 Taylor WilliamR, Stark GeorgeR. Regulation of the G2/M transition by p53. Oncogene 2001; 20: 1803-1815
  • 29 Ruppenthal SL, Noll A, Götz C. et al. Interference between p53 and cdc25C in cell cycle regulation. Int J Oncol 2007; 31: 345-352
  • 30 Brenner AnnetteK, Reikvam Håkon, Lavecchia Antonio. et al. Therapeutic targeting the cell division cycle 25 (CDC25) phosphatases in human acute myeloid leukemia-the possibility to target several kinases through inhibition of the various CDC25 isoforms. Molecules 2014; 19: 18414-18447
  • 31 Kenji Tamura, Eileen C. Southwick, Jeffrey Kerns et al. Cdc25 inhibition and cell cycle arrest by a synthetic thioalkyl vitamin K, analogue.Cancer Research March 1 2000; 60: 1317-1325