title: Chemopreventive evaluation of a Schiff base derived copper (II) complex against azoxymethane-induced colorectal cancer in rats.
abstract: 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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Maryam
authors.initials: M
authors.lastname: Hajrezaie
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Pouya
authors.initials: P
authors.lastname: Hassandarvish
authors.affiliation: Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Soheil Zorofchian
authors.initials: SZ
authors.lastname: Moghadamtousi
authors.affiliation: Department of Chemistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Nura Suleiman
authors.initials: NS
authors.lastname: Gwaram
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Shahram
authors.initials: S
authors.lastname: Golbabapour
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Abdrabuh
authors.initials: A
authors.lastname: Najihussien
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Amel Abdullah
authors.initials: AA
authors.lastname: Almagrami
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Maryam
authors.initials: M
authors.lastname: Zahedifard
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Elham
authors.initials: E
authors.lastname: Rouhollahi
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Hamed
authors.initials: H
authors.lastname: Karimian
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Somaye
authors.initials: S
authors.lastname: Fani
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Behnam
authors.initials: B
authors.lastname: Kamalidehghan
authors.affiliation: Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Nazia Abdul
authors.initials: NA
authors.lastname: Majid
authors.affiliation: Department of Chemistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Hapipah Mohd
authors.initials: HM
authors.lastname: Ali
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Mahmood Ameen
authors.initials: MA
authors.lastname: Abdulla
mesh_terms: D058739:Aberrant Crypt Foci / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001397:Azoxymethane / Q000009:adverse effects; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D018890:Chemoprevention; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D003300:Copper / Q000737:chemistry*; D004195:Disease Models, Animal; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D012545:Schiff Bases / Q000737:chemistry* / Q000494:pharmacology*; D023382:Toxicity Tests, Acute
chemical_list: D002273:Carcinogens; D018809:Proliferating Cell Nuclear Antigen; D012545:Schiff Bases; D003300:Copper; D001397:Azoxymethane