Comparing the Effect of Homocysteinylated and Normal Forms of Substance P on the Proliferation of PC12 Cell-line in the Presence of Cysteine

In the present study, the effects of homocysteinylated and normal forms of substance P were investigated on the proliferation of PC12 cell-line in the presence of cysteine. Cells were cultured in an RPMI-Glutamax medium containing 10% FBS and metabolic activity was assessed in the presence of different concentrations of peptide and cysteine using the MTT assay. Afterward, the morphological changes were determined using phase-contrast microscopy. In order to evaluate the protective effect of homocysteinylated peptide against H2O2, cells were treated with 150 µg/ml H2O2 for 3 h, and their nitric oxide production was assessed using the Griess colorimetric assay. findings showed that two forms of substance P, at selected concentrations, caused a significant increase in proliferation of PC12 cells and a decrease in the amount of NO production in response to H2O2 toxicity. At a concentration of 6-10 M, homocysteinylated and normal forms of substance P increased the rate of PC12 proliferation up to 78.65% and 38.55 % and decreased the levels of NO up to 36% and 14%, respectively. This indicates that homocysteinylated form of substance P is more potent (  than the normal form. The percentage of protection for homocysteinylated substance P was about 22% higher than the normal form. It seems that homocysteinylated substance P can increase the growth rate of cancer cells and promote the disease course through the reduction in NO production in pathological conditions.