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 micromol/L drinking water ad libitum) and 1alpha, 25-dihydroxy vitamin D(3) (Vitamin D(3)) (0.3 mug/100 muL 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 D(3) 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.
Department of Pharmaceutical Technology, Jadavpur University, PO Box 17028, Calcutta-700032, India.
Shaonly
S
Samanta
Mary
M
Chatterjee
Balaram
B
Ghosh
M
M
Rajkumar
Ajay
A
Rana
Malay
M
Chatterjee
D019813:1,2-Dimethylhydrazine; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D018736:DNA Adducts / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004357:Drug Synergism; D005455:Fluorescent Antibody Technique; D007700:Kinetics; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014639:Vanadium / Q000494:pharmacology*
D018736:DNA Adducts; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D014639:Vanadium; D002117:Calcitriol; D001973:Bromodeoxyuridine; D019813:1,2-Dimethylhydrazine