Type-2 diabetic serum effects on the growth and cell survival of cancer cells

Zahra Zahiri,1 Safoura sameni,2,* Seyedeh sara hashemi ,3

1. Department of Biochemistry, Shiraz Branch, Islamic Azad University, Shiraz, Iran
2. Department of Biochemistry, Shiraz Branch, Islamic Azad University, Shiraz, Iran
3. Burn & Wound Healing Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Introduction

Type 2 diabetes is a metabolic disorder characterized by increased glucose in the blood following an insulin resistance or insulin deficiency. different studies have shown high levels of caspase 3 and bax activity in diabetic patients. the high level of caspase 3 and bax induces apoptosis. in this study, serum levels of caspase 3 and bax were investigated in diabetic patients and their effects on growth and survival of cancer cells were compared to normal cells

Methods

the total number of 150 patients were selected for type 2 diabetes and 150 subjects for the control group. initially, different biochemical elements were evaluated in these individuals. for the first screening, 5 subjects with high blood glucose and the lowest serum level of zinc were enrolled in the diabetic population, and the control subjects with normal blood sugar levels and highest serum zn level were examined for the enzyme caspase 3 and bax levels by elisa. in the second stage of screening, those of diabetic individuals with the highest serum levels of caspase 3 and bax were chosen beside those control samples with the lowest levels of caspase 3 and bax, which the effect of all together were studied on the cell viability through the last step. finally, the cytotoxicity effect of selective serums was studied and compared during 24, 48 and 72 hours on the survival of hdf and fibroblast cells. the results were compared statistically

Results

For both control and type 2 diabetes mellitus groups, fbs and hba1c, triglycerides and cholesterol, hdl, ldl, bun, creatinine, as well as serum levels of zn were studied. in addition to calculating and comparing the mean and standard deviation for all data, this study clearly showed that there was a significant decrease (p≤0.05) in serum zn level in diabetic subjects compared to control group. in the second screening test, 5 samples were selected from each of the two groups and it was shown that serum levels of caspase 3 and bax (which also have an inverse association with zn level), has significantly increased in diabetes compared to the control group. finally, in the mtt assay, which was performed on two normal and hdf-fibroblast cells, showed that the survival of cancer cells after 24 hours of exposure was significantly declined by the diabetic serum compared to non-diabetic serum (p≤0.05).

Conclusion

The serum zn level of people with diabetes is lower compared to controls. serum levels of zn has a reverse relationship with caspase 3 and bax. by assessing the survival of fibroblasts and cancer cells, it was shown that after 24 hours of treatment, diabetic serum can significantly decrease the survival of cancer cells compared to normal cells, which is probably due to activity of caspases and other inducers of apoptosis in early hours of action

Keywords

Type 2 diabetes, cancer, caspase-3, bax, zn