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Published on: June 6, 2017
Induction of Cell Cycle Arrest in MKN45 Cells after Schiff Base Oxovanadium Complex Treatment Using Changes in Gene
Sara Mirjalili1, Maedeh Dejamfekr1, Abdolvahab Moshtaghian2
1Department of Biochemistry, 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.
Insights
Vanadium compounds significantly inhibit gastric cancer cell growth and migration. The schiff base oxovanadium complex induces cell cycle arrest at the G2/M phase, offering potential for new cancer therapies.
Area of Science:
- Inorganic Chemistry
- Medicinal Chemistry
- Cancer Biology
Background:
- Heavy metal compounds, including vanadium, nickel, and cobalt, show promise for disease treatment.
- Vanadium-containing compounds have demonstrated anticancer effects across various cell types.
- Gastric cancer remains a significant health concern, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the effects of a specific schiff base oxovanadium complex on gastric cancer cells (MKN45).
- To evaluate the complex's impact on cell cycle arrest, proliferation, and migration.
- To analyze the modulation of key genes involved in cell division (P53, GADD45, CDC25).
Main Methods:
- Cytotoxicity was assessed using cell viability assays.
- Cell cycle phase distribution was analyzed via propidium iodide (PI) staining and flow cytometry.
- Gene expression changes for P53, GADD45, and CDC25 were quantified.
Main Results:
- The schiff base oxovanadium complex significantly reduced MKN45 cell viability in a time- and concentration-dependent manner.
- Cancer cell migration and metastatic activities were inhibited by the complex.
- Cell cycle arrest at the G2/M phase was observed after 48 hours of treatment at 1 μg/ml.
- This arrest correlated with increased expression of P53 and GADD45, and decreased expression of CDC25.
Conclusions:
- Schiff base oxovanadium complex effectively inhibits the growth, proliferation, and migration of MKN45 gastric cancer cells.
- The complex induces G2/M phase cell cycle arrest, likely through DNA damage-mediated activation of cell division controllers.
- These findings highlight the therapeutic potential of vanadium-based compounds in gastric cancer treatment.
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