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

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.

Antitumor Properties of a New Macrocyclic Tetranuclear Oxidovanadium(V) Complex with 3-Methoxysalicylidenvaline Ligand

“…Up to now, the main proposed mechanism of action for the recently developed vanadium complexes involves ROS generation and DNA fragmentation [ 17 , 19 , 20 ]. Thus, to study the mechanism by which TetraV V induces tumor cell death, we firstly assessed the oxidative status and the DNA fragmentation percent in TetraV V -treated HepG2 cells compared to cisplatin.…”

“…Different organic ligands or some molecules possessing biological properties such as amino acids-derived Schiff bases were used to develop new vanadium (IV or V) complexes with pharmacological properties [ 6 , 13 , 14 , 15 , 16 ]. The anti-tumor activity of vanadium(V) complexes with organic ligands that have the ability to chelate through donor atoms, such as O, N, O’/O, N, N’/O, O’/N, O has been reported [ 9 , 14 , 17 , 18 , 19 ]. Some of these compounds have been shown to induce reactive oxygen species (ROS)-mediated apoptosis [ 14 ].…”

“…Some of these compounds have been shown to induce reactive oxygen species (ROS)-mediated apoptosis [ 14 ]. Additionally, DNA degradation appears to be the main mechanism of the anticancer activity of up to now developed vanadium compounds [ 14 , 19 ]. Moreover, the vanadium complexes seem to affect the cell cycle as a result of DNA degradation and ROS generation [ 14 , 19 , 20 ].…”

“…Additionally, DNA degradation appears to be the main mechanism of the anticancer activity of up to now developed vanadium compounds [ 14 , 19 ]. Moreover, the vanadium complexes seem to affect the cell cycle as a result of DNA degradation and ROS generation [ 14 , 19 , 20 ]. Furthermore, the apoptosis induced in pancreatic cancer cells by the corroboration between ROS and mitochondria dysfunction was recently proposed for an oxidovanadium(IV) complex [ 13 ].…”

In silico and in vitro analysis of FAK/MMP signaling axis inhibition by VO-clioquinol in 2D and 3D human osteosarcoma cancer cells

“…As it can be seen, that VO(CQ) 2 inhibited cell migration of bone cancer cells by 58% (2.5 µM) and 51% (10 µM), compared to 68% in untreated cells (p< 0.01). Some oxidovanadium(IV) compounds inhibit the cell migration of human cancer cells including stomach 31 , prostate 32 , bone 33 , breast and colorectal. 34…”