THE INSIGHT OF IN SILICO AND IN VITRO EVALUATION OF OYSTER MUSHROOM (PLEUROTUS OSTREATUS) AGAINST COLORECTAL CANCER TARGETING TIMP-1

Abstract

Targeted therapy treatment in Colorectal Cancer (CRC) works specifically on a protein or target cell in cancer. It plays a role in the survival of cancer cells. Targeted therapy involves several monoclonal antibodies, one of which is cetuximab which targets the Epidermal Growth Factor Receptor (EGFR). However, there are cases of cetuximab resistance caused by activities of the Tissue Inhibitor of Metalloproteinase-1 (TIMP-1). TIMP-1 can activate the downstream EGFR signaling pathway, thereby that TIMP-1 activities need to be inhibited. Polysaccharide compounds in Pleurotus ostreatus have potential as an immunomodulator and anticancer. This study aimed to determine the potential interaction, types of bonds, the binding energy between the polysaccharide compounds Pleurotus ostreatus and TIMP-1, and survival assay of human adenocarcinoma colorectal (HT-29) cells. This research method compounds selection, data mining, compounds and proteins preparation, docking and visualization of docking results, and cell viability assay. To the study results, TIMP-1 interacted with α-glucan, β-glucan, and galactomannan, which were mediated by hydrophobic and hydrogen bonds. We found new two-point interaction of TIMP-1 with α-glucan and β-glucan on Glu156 and Lys157 that plays a role in the interaction with CD63. Therefore, TIMP-1 can be a candidate for a new ligand on colon cancer targeted therapy. Cetuximab and Pleurotus ostreatus Extract (POE) combinations inhibited the survival of HT-29 cells. The α-glucan and β-glucan may partially inhibit TIMP-1 so that the possibility of resistance due to the interaction of TIMP-1 with CD63 can be inhibited and polysaccharide from Pleurotus ostreatus has anticancer activity on HT-29 cells.