The Effect of Curcumin on the Activity of MMP-17 and MMP-24 in Hepatocytes of Mice Exposed to Thioacetamide.

Abstract

Background: Hepatocellular carcinoma is the most primitive form of liver cancer, which is related to chemo carcinogens such as thioacetamide (TAA) and tissue remodeling molecules such as Matrix metalloproteinases (MMPs). Antioxidants, like curcumin (Cur), can inhibit these factors. In this research, the effect of curcumin on the expression and activity of two MMP enzymes, MMP-14 and MMP-17, which are involved in the carcinogenesis of mice after chronic exposure to thioacetamide, is investigated.

Methods: In this study, 30 mice were divided into six groups and studied for 4 months. The first group, control; the second group, curcumin; the third group, TAA; the fourth group, TAA and curcumin simultaneously; the fifth group, first treated with TAA for 2 months and then curcumin; and finally, the sixth group, first treated with curcumin for 2 months and then TAA. Afterward, the mice were euthanized, and their liver tissues were transferred to the laboratory for analysis of gene and protein expression.

Results: The averages of gene expression were calculated using SigmaPlot software and showed that the expression of MMP-17 and MMP-24 genes and the levels of their proteins were significantly increased by thioacetamide (****p < 0001) compared to the control group. Pathological observations indicated necrosis and dysplastic foci in the TAA group.

Conclusions: Considering the crucial roles of MMPs in various diseases, including hepatocellular carcinoma, the regulation of their gene expression and enzymatic activity is significant in preventing tumor progression. Compounds such as thioacetamide and polyphenols like curcumin can modulate the activity of MMP-17 and MMP-24.