Abstract.

Background: Colorectal cancer (CRC) is the third leading cause of cancer associated mortality worldwide. Current available chemotherapeutics against CRC have various disadvantages. Medicinal plants are source of many biologically active compound(s) which have potential for development as therapeutic agents against different types of cancer. The aim of the present study was to screen for effective novel therapeutic agents against CRC from natural medicinal plants and herbs.

Method:20 different plants from various species were collected randomly from various areas of Egypt. The cytotoxic and genotoxic effects against HCT-116 colon cancer cells was analyzed. Cytotoxicity was determined by MTT assay and comet assay was used to assess DNA damage. Gene expression was analyzed by qPCR for P53, Bcl2 and Bax.

Results:The results revealed that the methanolic extracts of Ononis vaginalis and Quercus robur L. showed significant cytotoxic effect against HCT116 cells in vitro in monolayer and multicellular cancer spheroids(MCS). Further investigation of methanolic extracts treated HCT116 cells revealed marked fold increase in the expression of p53, Bax, whereas Bcl2 expres‌sion was significantly decreased. Moreover, the methanolic extract of O.vaginalis induced more DNA damage to colon cancer cells(HCT-116), the results was confirmed by the visual score which indicated that most of the effect was gradual increase in the length of the comet tail in parallel with a decrease in nuclear DNA content. This variation in DNA damage accounted for the observed genotoxic effect of O.vaginalis on HCT-116 cells in-vitro. Also, the methanolic extract of O.vaginalis significantly inhibited tumor growth in Syngeneic tumor model in C26 injected mice compared with the vehicle control group. Conclusion: Collectively, the findings of the present study indicated that methanolic extract of O.vaginalis was able to decrease proliferation and promote apoptosis in colon cancer cells by inducing the p53/Bax mediated signaling pathway.Therefore, It may be used as a novel source of new antitumor agent in the treatment of CRC.