Chemoprevention of azoxymethane-initiated colon cancer in rat by using a novel polymeric nanocarrier--curcumin.
Curcumin is a potential natural anticancer drug with limited bioavailability due to the lack of solubility in aqueous solvents. The present study is designed to investigate the preventive effects of polymeric nanocarrier-curcumin (PNCC) on colon carcinogenesis in an azoxymethane-induced rat tumor. Forty rats were divided into control, curcumin- and PNCC-treated groups. Animals received azoxymethane (AOM) as a carcinogenic agent (15 mg/kg, s.c.) weekly for two consecutive weeks. They were given curcumin 0.2% and PNCC two weeks before till 14 weeks after the last injection of AOM. In the end, post euthanasia, the entire gastrointestinal tract was scrutinized for tumors, and the rest of the body for metastatic deposits. Tumor number, size and location were characterized. The histopathological and immunohistochemistry examinations were also performed on colon tissue. In vivo, curcumin nanoparticles inhibited colon cancer growth in animal model. The tumors incidence and number decreased by nanocurcumin comparison with control. Furthermore, the nuclear/cytoplasmic ratio, epithelial stratification, nuclear dispolarity, goblet depletion, structural abnormality, and the expression of Beta-catenin and Bcl-2 proteins were reduced in PNCC compared to others groups (P<0.05). In addition, Bax protein expression was significantly increased in PNCC in comparison with control and curcumin-treated groups (P<0.001). The present study demonstrated the potential anticancer effects of PNCC in a typical animal model. The results provide evidence that nanopolymeric curcumin exerts a significant chemopreventive effect on AOM-initiated colon cancer through cell proliferation inhibition and apoptosis induction. More investigations are needed to confirm its safety for human use.
Cancer Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran. aalizadeh@razi.tums.ac.ir
Ali Mohammad
AM
Alizadeh
Mahmood
M
Khaniki
Saleh
S
Azizian
Mohammad Ali
MA
Mohaghgheghi
Majid
M
Sadeghizadeh
Farhood
F
Najafi
D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage* / Q000737:chemistry; D001397:Azoxymethane / Q000633:toxicity*; D018890:Chemoprevention / Q000379:methods; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
D016588:Anticarcinogenic Agents; D004337:Drug Carriers; D011108:Polymers; D003474:Curcumin; D001397:Azoxymethane