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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

The Antitumor Activity of a Novel Fluorobenzamidine against Dimethylhydrazine- Induced Colorectal Cancer in Rats

Author(s): Mohammed Abdel-Rasol, Nadia M. El-Beih, Shaymaa M.M. Yahya, Mohamed A. Ismail and Wael M. El-Sayed*

Volume 20, Issue 4, 2020

Page: [450 - 463] Pages: 14

DOI: 10.2174/1871520619666191021162411

Price: $65

Abstract

Background: Colorectal cancer is among the leading causes of death worldwide. The incidence of deaths is expected to be 11.4 million in 2030.

Objective: We aimed to evaluate the in vitro and in vivo antioxidant and antitumor activities of a novel Bithiophene- Fluorobenzamidine (BFB) against DMH-induced colorectal cancer in rats.

Methods: The antiproliferative activity of BFB against HCT-116 colon cancer cells and apoptotic genes was assessed. In vivo study was also conducted in which 80 adult male rats were divided into 5 groups; control, BFB, and the other 3 groups were injected with DMH (20mg/kg, s.c., for 9 weeks). Group 4 was injected with 5 doses of cisplatin (2.5mg/kg, i.p over 21 weeks) and group 5 was injected with 3 doses/week of BFB (2.5mg/kg, i.p, for 21 weeks).

Results: BFB exhibited weak to moderate in vitro antioxidant activity. It had a strong antiproliferative activity with IC50 ~0.3µg/ml. BFB induced extrinsic apoptosis through the upregulation of FasL, TRAL, p53 and caspase-8, and intrinsic apoptosis through the downregulation of Bcl-2 and survivin. BFB decreased the tumor incidence, multiplicity and size and improved the decreased body weight. BFB also ameliorated the functions of kidney and liver and antioxidants deteriorated by DMH. BFB significantly improved the pathological changes caused by DMH in colon tissues.

Conclusion: BFB showed a very promising antitumor activity against colorectal cancer induced by DMH in rats without causing hepato- or nephrotoxicity.

Keywords: Colorectal cancer, bithiophene, cisplatin, apoptosis, antioxidants, nephrotoxicity, hepatotoxicity.

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