الفهرس | Only 14 pages are availabe for public view |
Abstract The present study aimed to evaluate the antioxidant and antiproliferative effect of ginger extract (GE) and a novel bithiophene (BT) against HCT-116 colon cell line and understand the molecular mechanism(s) through which BT and GE exert their antitumor activity. The results showed that GE had a good antioxidant capacity and higher DPPH˙ and hydroxyl radical scavenging abilities than the novel BT. BT was the most cytotoxic agent against HCT-116 cancer cell. GE and BT act as anticancer agent through upregulation of FasL, TRAIL, p53 and caspase-8 and downregulation of Bcl-2 and survivin genes. Rats were randomly divided into (8) groups. group 1 untreated control. group 2 left untreated for 9 weeks then treated with cisplatin (CP) (5 equal doses of 2.5 mg/kg, i.p.). group 3 left untreated for 9 weeks then treated with GE (300 mg/kg, p.o., 3 doses/week). group 4 left untreated for 9 weeks then treated with BT (2.5 mg/kg, i.p., 3 doses/week). group 5 was s.c injected with dimethylhydrazine (DMH) (20 mg/kg) for 9 weeks. Groups 6,7, and 8 administered DMH for 9 weeks then treated with CP, GE, or BT, respectively, for the remaining 21 weeks. Treatment of rats with DMH resulted in 100% tumor incidence and 2.3 tumor/rat. A significant elevation in serum ALT, urea and creatinine and a decreased in body weight gain. A significant decrease in hepatic GSH level, CAT, SOD, GST, GR activities and GSH content and γ-GT activity in kidney. Histopathological examination of colon of DMH-treated rats revealed adenomatous polyps with inflammatory reaction, polymorphism, clear mitosis, inflammatory cells infiltrating the mucosa and submucosa. Both muscularis and serosa were free from inflammatory cells but involved in cancer formation. Anaplastic changes and cystic formation together with few hemorrhage and inflammatory reaction infiltrating muscularis. GE and BT were able to mitigate all the previous injurious effects of DMH. The alleviation offered by GE and BT was better than that shown after CP administration. Thus, this study proved that GE and BT ameliorated the DMH induced-colon tumors and were hepatoprotective and renoprotective agents. |