Ginkgo biloba L. leaf extract offers multiple mechanisms in bridling N-methylnitrosourea - mediated experimental colorectal cancer

In Egypt, colorectal cancer (CRC) is the 6th cancer in both gender and CRC rates are high in subjects under 40 years of age. This study goaled to determine the development of CRC using relevant biochemical markers and to elucidate the potent mechanism of Ginkgo biloba L. leaf extract in retrogression of experimental CRC. Adult male Sprague-Dawley rats were administered N-methylnitrosourea (N-MNU; 2 mg in 0.5 ml water/rat) intrarectally thrice a week for five weeks to induce CRC, followed by treatment with either 5-fluorouracil (5-FU; 12.5 mg/kg, i.p.) or Ginkgo biloba L. leaf extract in a dose of 0.675 and 1.35 g/kg, p.o. respectively. The developed tumor enhanced plasma TGF-beta, and Bcl(2), serum EGF, CEA, CCSA, and MMP-7 significantly. Also, gene expression analysis showed significant upregulation of colonic beta-Catenin, K-ras and C-myc genes. Besides, immunohistochemical findings revealed significant increase in COX-2, cyclin D1 and survivin content in colon tissue. These data were further supported by the histological observations. Ginkgo biloba L. leaf extract-treated rats; particularly those treated with dose of 1.35 g/kg, exhibited significant reduction in the aforementioned parameters and improvement in the histological organization of the colon tissue. The therapeutic effect of Ginkgo biloba L. leaf extract was comparable with that mediated by 5-FU. The current research proved that Ginkgo biloba L. leaf extract could suppress tumor cell proliferation, promote apoptosis, and mitigat inflammation in vivo. The amelioration of these key events might be linked with the inhibition of Wnt/beta-Catenin signaling module. The outcomes of the present investigation encourage the use of Ginkgo biloba L. leaf extract as a complementary and alternative therapeutic approach to abate CRC.