ANTICANCER EFFECTS OF COUMARIN COMPOUNDS OSTHOLE AND IMPERATORIN, ALONE AND IN COMBINATION WITH 5-FLUOROURACIL IN COLON CARCINOMA CELLS

Colon cancer is one of the causes of cancer-related mortality. Therefore, more efficient therapy strategies are required. There is an increasing interest in natural products due to the potential cytotoxic activity in various cancer cell lines. Osthole and imperatorin are major active coumarins found in a variety of plants. The present study aimed to assess the cytotoxic effects of two natural coumarins, osthole, and imperatorin, administered separately and combined with 5-fluorouracil (5-FU) in human colon carcinoma cells and to identify the action of a mechanism. Real-time cell analysis with the xCELLigence System was used to screen for appropriate concentrations of osthole, imperatorin, 5-FU, and API-1 with cytotoxic or cytostatic potential and to monitor cell proliferation and viability in CoLo 205 cells continuously. Furthermore, the effects of the compounds on p38MAPK-alpha levels and the expression of Akt mRNA were evaluated. As a result, osthole showed considerable antiproliferative activity in CoLo 205 cells and increased the efficacy of 5-FU by accelerating the cytotoxic effect. Osthole was found to be as effective as protein kinase inhibitor API-1. Osthole, osthole+5-FU, and imperatorin treatments were significantly able to increase the ratio of phospho-p38MAPK-alpha/p38MAPK-alpha. It was demonstrated that osthole, 5-FU, and API-I+5-FU were significantly suppressed the Akt mRNA expression as positive control API-1. The findings indicate that osthole may be a promising anti-cancer agent in the treatment of colon cancer and may increase the efficacy of 5-FU and, therefore, may reduce common side effects of traditional chemotherapy in colon cancer with 5-FU.