Original Articles

Inhibitory Effect Of Zinc, Copper And Selenium On Telomerase Activity In Tumor Tissues And T47D Breast Cancer Cell Line

Abstract

Background: The present study was performed to investigate the effects of trace elements particularity Se, Zn and Cu on tumor genesis in breast cancer.Methods: The inhibitory effect of Se, Zn and Cu, on telomerase activity was analyzed in human breast tumor tissues and breast cancer (T47D) cells. Tissue specimens from 24 women with benign breast disease and 32 women with breast cancer specimens (ductal carcinoma, lobular carcinoma) were collected during surgery. In addition venous blood samples were obtained for assessing the trace elements. T47D cell line was cultured and treated with trace elements. Telomerase activity then was measured with TRAP assay in cell line and tissue extracts.Results: There was a significant difference between tissue and serum levels of Cu, Se and the ratio of Cu/Zn in patients and controls (P<0.001). After treating with 100 μm/L Zn So4, 10 μm /L Cu So4 for 6 hours, telomerase activity of T47D cells was markedly increased. But after treating with 10, and 30 μm /L selenium-L- methionin, telomerase activity was markedly inhibited. Telomerase activity of T47D cells for 24 hours were 0.93, 0.60 and for 48 hours were 0.76, 0.12 respectively (control 49.2℅). There were variations in serum level of Zn and Cu in breast cancer patients.Conclusion: Association between trace elements level and telomerase activity level can be exploited as prognostic and diagnostic marker for breast cancer.

Parkin D, Bray F, Ferlay J, Pisani P (2005). Global cancer statistics, 2002. CA Cancer J Clin. 55: 74–108.

Lee S, Park J, Park H (2008). Breast cancer risk factors in Korean women: a literature review. Int Nurs Rev. 55: 355-9.

Maria A, Arturo L, Chantal A (2006). Telomerase inhibition enhances the response to anticancer drug treatment in human breast cancer cells. Mol Cancer Ther. 5: 1669–75.

Zarghami N, Grass L, Diamandis E (1997). Steroid hormone regulation of prostate specific antigen expression in breast cancer. Br J Cancer. 75: 579-588.

Meng L, Rong F, Chun L, Ping Y, Ming M, Li J, Hong J, Feng Q (2007). Noninvasive Imaging of Human Telomerase Reverse Transcriptase (hTERT) Messenger RNA with 99mTc-Radiolabeled Antisense Probes in Malignant Tumors. The J of Nuclear Medicine. 48: 2028-36.

Katharine L, Robert F, Kefah M (2004). The mRNA expression of hTERT in human breast carcinomas correlates with VEGF expression. J of Carcinogenesis. 3:1.

Amal S, Rahima P, Chen L, Nichola C, Robert L, Gareth R, Tim D, Leroy S (2007). Telomerase subunits expression variation between biopsy samples and cell lines derived from malignant glioma. Brain research. 1134: 45-52.

Avilion AA, Piatyszek MA, Gupta J, Shay JW, Bacchetti S, Greider CW (1996). Human telomerase RNA and telomerase activity in immortal cell lines and tumor tissues. Cancer Res. 56: 645–650.

Blasco M, Rizen M, Greider C, Hanahan D (1996). Differential regulation of telomerase activity and telomerase RNA during multi-stage tumorigenesis. Nat Genet. 12:200–204.

Chan J, Oh W, Xie W, Regan M, Stampfer M, King I, Abe M, Kantoff P (2009). Plasma Selenium, Manganese Superoxide Dismutase, and Intermediate- or High-Risk Prostate Cancer. J Clin Oncol. [Epub ahead of print]. And neck cancer patients: An interpretive Review. J

Borek C (2004). Dietary antioxidants and human cancer. Integr Cancer Ther. 3:333-41.

Chen W, Cao X, Zhu R (2003). Effect of selenium dioxide on proliferation, apoptosis, and telomerase activity of human lung cancer cell line in vitro. Ai Zheng. 22: 927-31.

Alaejos M, D´az Romero, Romero C (2000). Selenium and Cancer. Some Nutritional Aspects. Nutrition. 16: 376 –383.

Witkiewicz-Kucharczyk A, Bal W (2006). Damage of zinc fingers in DNA repair proteins, a novel molecular mechanism in carcinogenesis. Oxicol Lett. 162:29–42.

Nemoto K, Kondo Y, Himeno S, Suzuki Y, Hara S, Akimoto M (2000). Modulation of Telomerase activity by zinc in human prostatic and renal cancer cells. Biochem Pharma. 59: 401-405.

Powell R (2000). The antioxidant properties of Zinc. J Nutr. 130: 1447-54.

Benanti J, Williams D, Robinson K, Ozer H, Galloway D (2002). Induction of extracellular matrix-remodeling genes by the senescence- associated protein APA-1. Mol Cell Biol. 22: 7385- 97.

Kim S, Kim J, Ko Y, Koo J, Chung H, Lee-Kim Y (2003). Changes in lipid peroxidation and antioxidant trace elements in serum of women with cervical intraepithelial neoplasia and invasive cancer. Nutr Cancer. 47: 126-30.

Bradford M (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72: 248–254.

Piccinini L, Borella P, Bargellini A, Medici C, Zoboli A (1996). A Case -control study on selenium, zinc, and copper in plasma and hair of subjects affected by breast and lung cancer. Biol Trace Element Res. 51: 23-30.

Feng P (2001). Zinc inhibits prostate cancer growth. The American society for cell biology 41st annual meeting . 8-12 Washington, DC.

Prasad S, Beck J, Doerr D, Shamsa F, Penny H, Marks S (1998). Nutritional and zinc status of head 35. Davis C, Uthus E (2003). Dietary folate and American Collage Nutr. 17: 409-418.

Karunasinghe N, Ferguson L, Tuckey J, Masters J (2006). Hemolysate thioredoxin reductase and glutathione peroxidase activities correlate with serum selenium in a group of New Zealand men at high prostate cancer risk. J Nutr. 13: 2232-5.

Silvia L, Anna M, Alessandra M, Medda (2005). Mechanism-based in activators of plant copper/quinone containing amine oxidases. Phytochemistry. 1751-1758.

Brewer J (2001). Copper Control as an Antiangiogenic Anticancer Therapy: Lessons from Treating Wilson S Disease. Exp Biol Med. 226: 665-73.

Ebert R, Ulmer M, Zeck S, Meissner-Weigl J, Schneider D (2006). Selenium supplementation restores the antioxidative capacity and prevents cell damage in bone marrow stromal cells in vitro. Stem Cells. 24: 1226-35.

Liu Q, Wang H, Hu D, Ding C, Xiao H, Xu H (2003). Effects of sodium selenite on telomerase activity and telomere length. Sheng Wu Hua Xue Yu Sheng Wu Li Xue Bao (Shanghai). 35: 1117-22. [In Chinese].

Ionescu J, Novotny J, Stejskal V, Latsch A, Blaurock-Busch E (2006). Increased levels of transition metals in breast cancer tissue. Neuro Endocrinal Lett. 1: 36-9.

Geraki K, Farquharson M, Bradley D (2004). X- ray fluorescence and energy dispersive x-ray diffraction for the quantification of elemental concentrations in breast tissue. Phys Med Biol. 49: 99-110.

Kuo H, Chen S, Wu C, Chen D, Lee J (2002). Serum and tissue trace elements in patients with breast cancer in Taiwan. Biol Trace Elem Res. 89: 1-11.

Gupta S, Singh S, Shukla V (2005). Copper, Zinc, and Cu/Zn Ratio in Carcinoma of the Gallbladder. Journal of Surgical Oncology. 91: 204–208.

Sherif L, Rizk, Howard H. Sky-Peck (1984). Comparison between Concentrations of Trace Elements in Normal and Neoplastic Human Breast Tissue1. Cancer research. 44: 5390-5394.

Tesmer V, Savre-Train I, Shay J, Wright W (1996). Both transcriptional and posttranscriptional mechanisms regulate human telomerase template RNA levels. Mol Cell Biol. 19: 3989–3997.

Nelson R, Davis F, Sutter E, Kikendall J, Sobin L, Milner J (1995). Serum selenium and colonic neoplastic risk. Dis. Colon Rectum. 38: 1306-1310 selenium affect dimethylhydrazine-induced aberrant crypt formation, global DNA methylation and onecarbon metabolism in rats. J Nutr. 133: 2907-14.

Files
IssueVol 3 No 1 (2011) QRcode
SectionOriginal Articles
Keywords
Breast cancer Zinc Copper Selenium Telomerase

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Zarghami N, Rahmati M, Mohajeri A, Pourhassan M, Asadi J. Inhibitory Effect Of Zinc, Copper And Selenium On Telomerase Activity In Tumor Tissues And T47D Breast Cancer Cell Line. Basic Clin Cancer Res. 1;3(1):14-22.