The Antitumor Activity of Ginger against Colorectal Cancer Induced by Dimethylhydrazine in Rats

Author(s):

Mohammed A. Abdel-Rasol, Nadia M. El-Beih, Shaymaa S. Yahya and Wael M. El-Sayed*   Pages 1601 - 1610 ( 10 )

Abstract:

<p>Background: Bowl or colorectal cancer (CRC) is the third most common type of cancer with about two million new cases every year. CRC is the second leading cause of cancer related mortalities. <p> Objective: The study aims to evaluate the anticancer activity of ethanolic Ginger Extract (GE) in HCT-116 colon cells and colorectal tumors induced by dimethylhydrazine (DMH). <p> Methods: The antiproliferative activity was measured by MTT assay and the gene expression was assessed by q-RTPCR. For the antitumor study, rats were divided into five groups in random; control, group two was orally treated with 300 mg/kg of GE for 21 weeks, group three was s.c. injected with DMH (20 mg/kg) for 9 weeks, and groups four and five were treated with DMH and then treated with cisplatin (2.5 mg/kg, i.p) or GE, respectively, for 21 weeks. <p> Results: GE had a significant antiproliferative activity with IC₅₀~ 12.5 &#181;g/ml. GE induced both extrinsic and intrinsic apoptotic pathways. GE induced the expression of FasL, TRAIL, p53, and caspase-8 and downregulated Bcl-2 and survivin genes. Treatment of rats with DMH resulted in 100% tumor incidence and 2.3 tumors/rat. DMH significantly elevated the serum ALT, urea, and creatinine and significantly decreased the body weight gain. DMH also caused significant reductions in the hepatic GSH level, and the activities of catalase, SOD, GST, and GR in the liver as well as the renal GSH content and &#947;-GT activity. The colon from rats insulted with DMH showed adenomatous polyps with polymorphism and mitosis. The mucosa and submucosa were infested with inflammatory cells while serosa and muscularis were devoid from these cells. However, the muscularis was infiltrated with cystic formation, anaplastic changes, and hemorrhage. GE was able to alleviate all the previous deleterious effects of DMH and it was superior to cisplatin in its ameliorative effects. It did so without eliciting hepatotoxicity or nephrotoxicity which were shown in the group treated with DMH and cisplatin. <p> Conclusion: This study proved that the antitumor activity of GE against the DMH induced-CRC is superior to cisplatin. GE was also safer than cisplatin and did not elicit hepatotoxicity or nephrotoxicity. GE induced apoptosis and has carcinostatic activity.</p>

Keywords:

Colorectal cancer, HCT-116, apoptosis, tumor incidence, oxidative stress, nephrotoxicity, hepatotoxicity.

Affiliation:

Department of Zoology, Faculty of Science, University of Ain Shams, Abbassia 11566, Cairo, Department of Zoology, Faculty of Science, University of Ain Shams, Abbassia 11566, Cairo, Department of Hormones, National Research Centre, Dokki 12622, Giza, Department of Zoology, Faculty of Science, University of Ain Shams, Abbassia 11566, Cairo

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