Protective Effect of Crocin on Cadmium Induced-Overexpression of Matrix Metalloproteinases (MMPs) Gene Family in Rat Liver

Abstract

Background: Metal pollutants such as Cadmium are known as carcinogenic agents and correlated with metastatic potential and tumor aggressiveness. Matrix metalloproteinases (MMPs) are taken into account as the focal points of metastasis. Crocin, a carotenoid chemical compound in Saffron, has been proved to have anti-cancerous properties. However, there is no reliable evidence yet to prove its anti-metastatic activity. Objective: The evaluation of the protective effect of Crocin against Cadmium through monitoring the expression of MMP genes. Materials and Methods: The in-silico analysis based on the GEO database was done for purposefully choosing MMPs. At the wet lab step, after 8 weeks of treatment of the animal (40 female Wistar rats divided into four groups of 10) with Cadmium, Crocin, complex (Cadmium+Crocin) and placebo (control), RNA extraction followed by cDNA synthesizing was done from rats’ liver tissues. Using primers for MMP genes (MMP-1, 3, 7, 12 and 13), the relative fold change of gene expression was studied. Ultimately, the statistical analysis determined the difference in gene expression between groups. Results: Cadmium significantly upregulated the selected MMP genes in comparison with controls. In contrast, Crocin significantly downregulated the expression of all studied MMP genes. Complex administration of Cadmium and Crocin displayed a controlled increase of expression in all MMPs except MMP-1, which was lower than the Cadmium group. Conclusion: These results indicated that the elevation of MMPs expression level by Cadmium was significantly suppressed by Crocin. This could promisingly demonstrate that Crocin possesses a modulating role in inhibiting overexpression of MMPs that might be considered as the anti-metastatic agent.