Inhibition of matrix metalloproteinase gene expression as mechanism of anti-angiogenic activity of Holothuria atra methanolic extract on human colorectal carcinoma cell lines (HCT-116 and HT-29)

Abstract

Marine natural products contain a wide range of bioactive compounds with therapeutic properties that are potential candidates for drug development. In cancer, anti-angiogenic therapy is being utilized to eradicate primary tumor tissues and suppress tumor metastasis. This study determined the cytotoxicity of Holothuria atra crude methanolic extract on HCT-116 and HT-29 human colorectal carcinoma cell lines and its effect on the expression of the matrix metalloproteinase (MMP) gene as an angiogenic inhibitor. Results show that H. atra extract has a significant cytotoxic activity against both HCT-116 and HT-29 cells and is comparable with the positive control chemotherapy drug 5-Fluorouracil. Real time RT-PCR and gel analysis showed that MMP-13 gene was down-regulated in treated samples for both cell lines. This supported the hypothesis that H. atra extract can act as an angiogenic inhibitor of colorectal carcinoma cells by suppressing MMP gene expression.