Antiproliferative and anti-inflammatory properties of diindolylmethane and lupeol against N-butyl-N-(4-hydroxybutyl) nitrosamine induced bladder carcinogenesis in experimental rats.

Abstract

Chemoprevention may involve perturbation of a variety of steps in tumor initiation, promotion, and progression. To investigate the antiproliferative and anti-inflammatory potential effects of diindolylmethane (DIM) and lupeol on experimental bladder carcinogenesis. Sixty healthy male Wistar rats were selected and randomly divided into six groups, with 10 rats in each group. Group I: control; group II: N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN; 150 mg/gavage/twice a week) for 8 weeks, and then they were given 100 ppm concentrations of dimethylarsenic acid (DMA) in the drinking water for 28 weeks; group III: BBN + DMA + DIM (5 mg/kg body weight (b.w.)/day) treatment was started after BBN treatment, and it was orally administered for 28 weeks); group IV: BBN + DMA + lupeol (50 mg/kg b.w./day) treatment was started after BBN treatment, and it was orally administered for 28 weeks); and groups V and VI: DIM and lupeol treatment alone for 36 weeks. Bladder tissues were collected after 36th week study protocol for further analysis. Our results revealed that DIM and lupeol treatment showed inhibition of tumor growth in the bladder by histopathological confirmations as well as significantly (p < 0.001) increased the expression of phosphotensin (PTEN) and significantly (p < 0.001) decreased the expression of tumor necrosis factor α, nuclear factor κβ (p65) were quantified using Western blot analysis. DIM and lupeol treatment significantly (p < 0.001) decreased the levels of Cox-2 in bladder tissue samples and NMP 22 in urine samples were quantified using enzyme-linked immunosorbent assay method. Preventive DIM and lupeol administration act as potent Cox-2 inhibitors, which activates the tumor suppressor protein PTEN against experimental bladder carcinogenesis by antiproliferative and anti-inflammatory properties.