Umbelliprenin is a sesquiterpene coumarin with vitro anti-carcinogenic activities. The aim of this study was to investigate the antitumor effects of umbelliprenin in animal models of colorectal cancer. The cytotoxic effects of umbelliprenin were explored on CT26 and L929by MTT assay. In this study, colorectal tumors developed in mice by intradermal injection of CT26 cell line. Tumor size, serum levels of IFN-γ and IL-4 by ELISA, and Ki-67, MMP2, MMP9, VEGF and E-cadherin markers by IHC method were evaluated. The results showed that umbelliprenin inhibited the cancer cells in a concentration-dependent manner. IC50 Evaluation showed that L929 cells were more resistant to Umbelliprenin than CT26 cells. Umbelliprenin treatment in both tumor-bearing mice and control normal mice showed significantly increased IFN-γ and decreased IL-4(P < 0.05). The pathologic findings had shown that the E-cadherin marker in the umbelliprenin treated cancerous mice were significantly higher compared to the control group (P < 0.05) while the expression of Ki-67 marker was reduced significantly (P < 0.05). Markers involved in angiogenesis including VEGF, MMP2, and MMP-9 in the cancerous mice group treated with umbelliprenin showed a significant decrease compared to the control group (P < 0.05). Metastasis to lung and liver was reduced in umbelliprenin treated group. Our results showed that umbelliprenin inhibited CT26 tumor cells in-vitro. The in-vivo reduction of tumor size, angiogenesis, and proliferation markers and the absence of metastasis represents the antitumor effects of umbelliprenin on colorectal cancer. The results showed that umbelliprenin can be considered as a good candidate for the treatment of colorectal cancer.
Keywords: Anti-angiogenesis; Anti-carcinogenic effect; CT26; Colorectal cancer; Immunohistochemistry; Umbelliprenin; cytotoxic effect.