Vanadium and 1, 25 (OH)2 vitamin D3 combination in inhibitions of 1,2, dimethylhydrazine-induced rat colon carcinogenesis

The current investigation demonstrates the antitumor effects of combined Supplementations of vanadium (V) (4.27 mu mol/L drinking water ad libitum) and1 alpha, 25-dihydroxy vitamin D-3 (Vitamin D3) (0.3 mu g/100 mu L propylene glycol per os twice a week) on 1, 2 dimethylhydrazine (DMH) (20 mg/kg body weight) induced rat colon carcinogenesis. There was a significant reduction in incidence (70%), multiplicity (P<0.0001) and volume (P<0.01) of colon tumors. HPLC-fluorescence assay detected the combinatorial actions of V and Vitamin D-3 against DMH-induced colonic O-6-methylguanine DNA adducts formation (at four sequential time points; ANOVA, F= 13,56, P<0.01). Simultaneous inhibition of DNA single strand breaks (P<0.001) indicates the potency of the combination regimen in limiting the initiation event of colon carcinogenesis. Immunohistochemical analysis revealed that the effect of V and vitamin D3 occurred through suppression of cell proliferation (BrdU-LI: P<0.001) along with an induction of apoptosis (TUNEL-LI: P<0.01). The immunoexpression of tumor suppressor p53 and downregulation of antiapoptotic protein BCl-2 in subsequent immunofluorescence assay further provide strong evidence for the combinatorial inhibitory actions of vanadium and vitamin D-3 against DMH-induced rat colon carcinogenesis. (C) 2008 Elsevier B.V. All rights reserved.