Chemopreventive Evaluation of a Schiff Base Derived Copper (II) Complex against Azoxymethane-Induced Colorectal Cancer in Rats

Autor: Shahram Golbabapour, Hamed Karimian, Maryam Zahedifard, Hapipah Mohd Ali, Pouya Hassandarvish, Soheil Zorofchian Moghadamtousi, Nazia Abdul Majid, Abdrabuh NajiHussien, Elham Rouhollahi, Amel Abdullah Almagrami, Nura Suleiman Gwaram, Maryam Hajrezaie, Somaye Fani, Mahmood Ameen Abdulla, Behnam Kamalidehghan
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Male
Pathology
medicine.medical_treatment
Cancer Treatment
lcsh:Medicine
Pharmacology
Kidney
Biochemistry
chemistry.chemical_compound
Aberrant Crypt Foci
Molecular Cell Biology
lcsh:Science
Saline
chemistry.chemical_classification
Multidisciplinary
biology
Chemistry
Glutathione peroxidase
Cancer Risk Factors
Colon Adenocarcinoma
Animal Models
Malondialdehyde
Oncology
Liver
Medicine
Female
Colorectal Neoplasms
Oxidation-Reduction
Aberrant crypt foci
Research Article
Biotechnology
medicine.medical_specialty
Drugs and Devices
Histology
Drug Research and Development
Immunology
Azoxymethane
Chemoprevention
Superoxide dismutase
Inorganic Chemistry
Model Organisms
In vivo
Proliferating Cell Nuclear Antigen
Gastrointestinal Tumors
medicine
Toxicity Tests
Acute
Animals
Biology
Schiff Bases
lcsh:R
Body Weight
Cancer
Cancers and Neoplasms
Chemotherapy and Drug Treatment
medicine.disease
Rats
Disease Models
Animal
biology.protein
Carcinogens
Rat
lcsh:Q
Blood Chemical Analysis
Copper
Zdroj: PLoS ONE
PLoS ONE, Vol 9, Iss 3, p e91246 (2014)
ISSN: 1932-6203
Popis: Background: Based on the potential of Schiff base compounds to act as sources for the development of cancer chemotherapeutic agents, this in vivo study was performed to investigate the inhibitory properties of the synthetic Schiff base compound Cu(BrHAP)2 on colonic aberrant crypt foci (ACF). Methodology: This study involved five groups of male rats. The negative control group was injected with normal saline once a week for 2 weeks and fed 10% Tween 20 for 10 weeks, the cancer control group was subcutaneously injected with 15 mg/kg azoxymethane once per week for two consecutive weeks, the positive control group was injected with 15 mg/kg azoxymethane once per week for two consecutive weeks and 35 mg/kg 5-fluorouracil (injected intra-peritoneally) for 4 weeks, and the experimental groups were first injected with 15 mg/kg azoxymethane once per week for two consecutive weeks and then fed 2.5 or 5 mg/kg of the Schiff base compound once a day for 10 weeks. Application of the Schiff base compound suppressed total colonic ACF formation by up to 72% to 74% (P,0.05) when compared with the cancer control group. Analysis of colorectal specimens revealed that treatments with the Schiff base compound decreased the mean crypt scores in azoxymethane-treated rats. Significant elevations of superoxide dismutase, glutathione peroxidase and catalase activities and a reduction in the level of malondialdehyde were also observed. Histologically, all treatment groups exhibited significant decreases in dysplasia compared to the cancer control group (P,0.05). Immunohistochemical staining demonstrated down-regulation of the PCNA protein. Comparative western blot analysis revealed that COX-2 and Bcl2 were up-regulated and Bax was down-regulated compared with the AOM control group. Conclusion: The current study demonstrated that the Cu(BrHAP)2 compound has promising chemoprotective activities that are evidenced by significant decreases in the numbers of ACFs in azoxymethane-induced colon cancer.
Databáze: OpenAIRE
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