Expression of Metallothionein, P53 and Antioxidant Enzymes by Selenium and Vitamin D3 during Diethyl Nitrosamine-Induced Rat Liver Preneoplasia Effect of selenium on nitrosamine-induced rat liver preneoplasia
Iranian Journal of Pharmaceutical Sciences,
Vol. 6 No. 2 (2010),
1 April 2010
,
Page 115-124
https://doi.org/10.22037/ijps.v6.41257
Abstract
Many studies have proved that the dietary micronutrient has an inhibitory effect against experimentally induced rat hepatocarcinogenesis. The present work is an attempt to understand combined effect of selenium (Se) and vitamin D3 (vit D3) on some potential protein expression markers of carcinogenesis, such as metallothionein (MT), P53 and antioxidant levels during diethyl nitrosamine (DEN) induced (200
mg/kg in 0.9% NaCl; IP) rat liv er preneoplasia. In a short term regimen combined supplementation of Se and vit D3 at a dose of 8 ppm in water and 0.3 μl/100μl in propylene glycol, respectively, suppressed the formation of DNA comets (28.40%), thereby indicating its non- genotoxicity at this particular dose. Se and vit D3 administration throughout the study reduced relative liver weight. Modular incidence were 22.7% when compared to the carcinogen control. However, treatment with Se and vit D3 showed significant expressions of MT and P53 which studied at four sequential time points. An increased immunopositive of P53 protein (1.3±0.56% p<0.02) was found in Se and vit D3 together treated rat liver with an elevated apoptotic labeling index (A1; p<0.001) as documented by TUNEL assay. The positive results of MT expression at various time intervals suggest that, Se and vit D3 together mediated suppression of MT may be associated with induction of apoptosis. The results thus provide evidence for the first time in support of the
potential role of combined supplementation of Se and vit D3 on induction of P53 apoptosis with concurrent suppression of MT in order to have an understanding. Regardless of the mechanism, based on the results reported in this study, both Se and vit D3 could be considered a potential cancer chemopreventive agents whose effect is presumably based on inhibition of growth of the neoplastic cells by coordinated regulations of different biochemical markers and enzymes studied herein.
- Antioxidant Enzymes
- Cancer
- Metallothionein
- P53
- Selenium
- Vitamin D3.
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References
[2] Thirumoorthy N, Manisenthil Kumar KT, Sundar AS, Panayappan L, Chatterjee M. Metallothionein: an overview. World J Gastroenterol 2007; 13: 993-6.
[3] Margoshes M, Vallee BL. A cadmium protein from equine kidney cortex. J Am Chem Soc 1957; 79: 4813-4.
[4] Kaplan LA, Pesce AJ, Kazmierczak SC. TOPIC OF THE REFERNCE. Clinical Chemistry Mosby: 2003; 4: pp. 960-72.
[5] Chakraborty T, Samanta S, Ghosh B, Thirumoorthy N, Chatterjee M. Vanadium induces apotosis and modulates the expression of metallothionein, Ki-67 nuclear antigen and P53 during 2-acetylamino fluorine induced rat liver pre neoplasia. J Biochem 2005; 94: 744-62.
[6] Jin R, Bay BH, Chow VTK, Tan PH, Lin VCL. Metallothionein IE mRNA is highly expressed in estrogen receptor-negative human invasive ductal breast cancer. Br J Cancer 2000; 83: 319-23.
[7] Deng DX, Chakrabarti S, Waalkes MP, Cherian MG. Metallothionein and apoptosis in primary human hepatocellular carcinoma and metastatic carcinoma. Histopathology 1998; 32; 348–55.
[8] Chatterjee M. Vitamin D and genomic stability. Mutation Res 2001; 475: 69-88.
[9] Abdel-Mageed AB, Agrawal KC. Activation of nuclear factor kappa B: potential role in metallothionein-mediated mitogenic response. Cancer Res 1998; 58: 2335-38
[10] Jayasurya A, Bay BH, Wim-Yap, NG Tan NG.Correlation of MT expression with apoptosis in nasopharyngeal carcinoma. Br J Cancer 2000; 82:1198-203.
[11] Donnelly ET, Bardwell H, Thomas GA, Williams ED, Hoper M, Crowe P, McCluggage WG, Stevenson M., Phillips DH, Hewer A, Osborne MR, Campbell FC. MT crypt-restricted immunopositivity indices (MT CR II) correlate with aberrant crypt foci (ACF) in mouse colon. Br J Cancer 2005; 2: 2160-5.
[12] Tan Y, Sinniah R, Bay BH, Singh G. Metallothionein expression and nuclear size in benign, borderline, and malignant serous ovarian tumours. J Pathol 1999; 189: 60-5.
[13] Kondo Y, Woo ES, Michalska AE, Choo KH, Lazo JS. Metallothionein null cells have increased sensitivity to anticancer drugs. Cancer Res 1995;55: 2021-3.
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