Evaluation of Antioxidant, Anticancer and Immunomodulatory Activities of Wild Carrot (Daucus carota ssp. carota) Oil and its Fractions.

Daucus carota L. ssp. carota, also known as wild carrot, has been used in traditional medicine in Lebanon to treat several diseases including cancer. The aim of the present study was to characterize the chemical constituents of D. carota oil extract (DCOE) and evaluate its anticancer activity. DCOE was chromatographed on silica gel column and four fractions were obtained. GC-MS and HPLC analysis of DCOE and fractions showed the presence of several sesquiterpenes and phenolic compounds. A major finding was the identification of 2-himachalene-6-ol, a sesquiterpene reported for the first time from wild carrot plant species. In vitro antioxidant activity of DCOE and its fractions was demonstrated and correlated to the phenolic and flavonoid contents. In vivo antioxidant and hepatoprotective activities of DCOE fractions was also observed in CCl14-induced hepatotoxicity in mice. The anticancer effects of DCOE and its fractions were evaluated against several human cancer cell lines and found to exhibit dose dependent anti-proliferative activities, with F1 and F2 demonstrating the highest cytotoxicity. The inhibition of cell growth by F1 or F2 fractions was mainly due to cell cycle arrest and apoptotic cell death as assessed by flow cytometry analysis and western blot analysis of several pro-apoptotic and anti-apoptotic proteins. Additionally, the induction of apoptosis was mediated through the inhibition of both MAPK/Erk and P13K/Akt pathways in human colon cancer cells (HT-29) and only through MAPK/Erk pathway in human breast cancer cells (MDA-MB-231). The antitumour promoting effect of F2 was illustrated by significant decrease in tumour incidence, yield and volume in DMBA/TPA- induced mouse skin carcinogenesis. Also, DCOE and fractions exhibited in vivo immunomodulatory effects through enhancing the release of immunomediators. In conclusion, the present study confirms the anticancer activity of wild carrot which can be considered as a potential remedy against various types of cancer with limited toxicity