title: Suppression of cell proliferation, induction of apoptosis and cell cycle arrest: chemopreventive activity of vanadium in vivo and in vitro.
abstract: In the present study, the authors evaluated the anticancer mechanism of vanadium, a dietary micronutrient and an important pharmacological agent, on a defined model of chemically induced rat mammary carcinogenesis in vivo and on human breast cancer cell line MCF7 in vitro. Female Sprague-Dawley rats were treated with 7,12-dimethylbenz(alpha)anthracene (0.5 mg/100 g body weight) by a single tail vein injection in an oil emulsion to induce mammary preneoplasia. Vanadium (ammonium monovanadate) at a concentration of 0.5 ppm (4.27 micromol/l) was supplemented in drinking water and given ad libitum to the experimental groups for 24 weeks. Histological finding showed substantial repair of hyperplastic lesions. There was a significant reduction in incidence, multiplicity (34%, p < 0.01), size of palpable mammary tumors and delay in mean latency period of tumor appearance. Immunohistochemical analysis in vivo indicated a decrease in cell proliferation (24.68% p < 0.05) and an increase among the TUNEL-positive apoptotic cells along with strong expressions of p53 and Bax, and downregulation of Bcl2 proteins in the mammary tissue of vanadium-treated animals. Further, MCF7 cells were cultured in minimal essential medium and were treated with 100, 175 and 250 microM of vanadium (ammonium monovanadate) for 36 hr. Exposure of MCF7 cells to vanadium led to induction of apoptosis in a dose-dependent manner. It was found further that vanadium treatment brought about a prominent cell cycle arrest and chromosomal condensation, leading to apoptosis (42.62%, p < 0.05). Results of both the in vivo and in vitro study demonstrate that vanadium has the potential to be developed into an anti-breast cancer drug in the near future.
authors.affiliation: Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
authors.forename: Rajarshi Sankar
authors.initials: RS
authors.lastname: Ray
authors.forename: Balaram
authors.initials: B
authors.lastname: Ghosh
authors.forename: Ajay
authors.initials: A
authors.lastname: Rana
authors.forename: Malay
authors.initials: M
authors.lastname: Chatterjee
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002273:Carcinogens / Q000633:toxicity; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000517:prevention & control; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D017968:Vanadium Compounds / Q000627:therapeutic use*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D002273:Carcinogens; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D017968:Vanadium Compounds; D051028:bcl-2-Associated X Protein; D015127:9,10-Dimethyl-1,2-benzanthracene