CYTOTOXIC EFFECTS OF ARIPIPRAZOLE ON MKN45 AND NIH3T3 CELL LINES AND GENOTOXIC EFFECTS ON HUMAN PERIPHERAL BLOOD LYMPHOCYTES
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Published on: September 13, 2017
Mohammad Shokrzadeh1, Abbas Mohammadpour1, Mona Modanloo1
1Mazandaran University of Medical Sciences, Faculty of Pharmacy, Department of Toxicology, Sari, Iran.
Background:
Gastric cancer is known as the fourth most common cancer. Current treatments for cancer have damaged the sensitive tissues of the healthy body, and in many cases, cancer will be recurrent. Therefore, need for treatments that are more effective is well felt. Researchers have recently shifted their attention towards antipsychotic dopamine antagonists to treat cancer. The anticancer activities of aripiprazole remain unknown.
Objective:
This study aimed to evaluate the efficacy and safety of aripiprazole on gastric cancer and normal cell lines.
Methods:
In this regard, the cytotoxicity and genotoxicity of aripiprazole were investigated in MKN45 and NIH3T3 cell lines by methyl tetrazolium assay and on peripheral blood lymphocytes by micronucleus assay. For this purpose, cells were cultured in 96 wells plate. Stock solutions of aripiprazole and cisplatin were prepared. After cell incubation with different concentrations of aripiprazole (1, 10, 25, 50, 100 and 200 μL), methyl tetrazolium solution was added. For micronucleus assay fresh blood was added to RPMI culture medium 1640 supplemented, and different concentrations of aripiprazole (50, 100 and 200 μL) were added.
Results:
The finding of present study showed that the IC50 of aripiprazole in the cancer cell line (21.36 μg/mL) was lower than that in the normal cell line (54.17 μg/mL). Moreover, the micronucleus assay showed that the frequency of micronuclei of aripiprazole at concentrations below 200 μM was much less than cisplatin.
Conclusion:
Aripiprazole can be a good cytotoxic compound and good candidate for further studies of cancer therapy.
Insights
Aripiprazole demonstrates significant cytotoxic effects against gastric cancer cells, showing higher efficacy and lower toxicity compared to normal cells. This antipsychotic may offer a promising new avenue for cancer therapy research.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Gastric cancer is a leading cause of cancer mortality, with current treatments often causing significant side effects and recurrence.
- Novel therapeutic strategies are urgently needed to improve cancer treatment outcomes.
- Antipsychotic dopamine antagonists are emerging as potential anticancer agents, though their efficacy is largely unexplored.
Purpose of the Study:
- To investigate the anticancer potential of aripiprazole.
- To evaluate the cytotoxicity and genotoxicity of aripiprazole in gastric cancer and normal cell lines.
Main Methods:
- Cytotoxicity was assessed using the methyl tetrazolium assay on MKN45 (gastric cancer) and NIH3T3 (normal) cell lines.
- Genotoxicity was evaluated by the micronucleus assay on peripheral blood lymphocytes.
- Cells were exposed to varying concentrations of aripiprazole and cisplatin (positive control).
Main Results:
- Aripiprazole exhibited a lower IC50 value in the gastric cancer cell line (21.36 μg/mL) compared to the normal cell line (54.17 μg/mL), indicating selective cytotoxicity.
- The micronucleus assay revealed a significantly lower frequency of micronuclei with aripiprazole at concentrations below 200 μM compared to cisplatin, suggesting reduced genotoxicity.
Conclusions:
- Aripiprazole displays promising cytotoxic properties against gastric cancer cells.
- Its selective action and lower genotoxicity profile make it a potential candidate for further investigation in cancer therapy.
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