Effect of teicoplanin on the expression of c-myc and c-fos proto-oncogenes in MCF-7 breast cancer cell line


Department of Genetics and Molecular Biology, Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Noncommunicable Disease, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran


Background: Teicoplanin is a member of vancomycin-ristocetin family of glycopeptide antibiotics. It mediated wound healing by increasing neovascularization possibly through activation of MAP kinase signaling pathway. The aim of this study is an evaluation of c-myc and c-fos genes expression after treatment of cells by teicoplanin and determines whether this glycopeptide antibiotic exerts its proliferation effects by influencing the expression of these genes. Hence, this study was designed to elucidate one possible mechanism underlying teicoplanin effects on cell proliferation using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay.
Materials and Methods: Breast cancer cell line, MCF-7, was cultured, and three different concentrations of teicoplanin were added to the plates. We measured the cell proliferation rate by MTT assay. After cell harvesting, total RNA was extracted to synthesize single-stranded cDNA. Real-time polymerase chain reaction was performed, and the data were analyzed.
Results: It was observed that the level of c-fos and c-myc genes' expressions was decreased at all three different concentrations of teicoplanin.
Conclusion: it could be concluded that although teicoplanin is considered as an enhancing cell growth and proliferation, but probably its effect is not through MAP kinase signaling pathway or perhaps even has inhibitory effect on the expression of some genes such as c-myc and c-fos in this pathway. Hence, the mechanism of action of teicoplanin for increasing cell propagation, through cell signaling pathways or chromosomal abnormalities, remains unclear, and further studies should be conducted.


Brogden RN, Peters DH. Teicoplanin. A reappraisal of its antimicrobial activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1994;47:823-54.  Back to cited text no. 1
King DW, Smith MA. Proliferative responses observed following vancomycin treatment in renal proximal tubule epithelial cells. ToxicolIn Vitro 2004;18:797-803.  Back to cited text no. 2
Lodish HF, Berk A, Kaiser CA, Krieger M, Bretscher A, Ploegh H, et al. Molecular Cell Biology. New York: WH Freeman; 2013.  Back to cited text no. 3
Evan GI, Littlewood TD. The role of c-myc in cell growth. Curr Opin Genet Dev 1993;3:44-9.  Back to cited text no. 4
Blackwood EM, Eisenman RN. Max: A helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. Science 1991;251:1211-7.  Back to cited text no. 5
Marcu KB, Bossone SA, Patel AJ. Myc function and regulation. Annu Rev Biochem 1992;61:809-60.  Back to cited text no. 6
Milde-Langosch K. The Fos family of transcription factors and their role in tumourigenesis. Eur J Cancer 2005;41:2449-61.  Back to cited text no. 7
Chiu R, Boyle WJ, Meek J, Smeal T, Hunter T, Karin M. The c-Fos protein interacts with c-Jun/AP-1 to stimulate transcription of AP-1 responsive genes. Cell 1988;54:541-52.  Back to cited text no. 8
Kashkooli Nezhad Koohi TK. Teicoplanin Effect on CHO, MCF-7 and Jurkat Cells' Growth and Cutaneous Wound Healing in Rats 1st International and 13th Iranian Genetics Congress; Iran, Tehran; 2014.  Back to cited text no. 9
Campoli-Richards DM, Brogden RN, Faulds D. Teicoplanin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential. Drugs 1990;40:449-86.  Back to cited text no. 10
Thompson G, Smith J, Kenny M, Dulwoeth J, Kulmala H, Yuh L. Pharmacokinetics of teicoplanin upon multiple dose administration to normal healthy male volunteers. Biopharm Drug Dispos 1992;33:213-20.  Back to cited text no. 11
Sirotkovic-Skerlev M, Krizanac S, Kapitanovic S, Husnjak K, Unusic J, Pavelic K. Expression of c-myc, erbB-2, p53 and nm23-H1 gene product in benign and malignant breast lesions: Coexpression and correlation with clinicopathologic parameters. Exp Mol Pathol 2005;79:42-50.  Back to cited text no. 12
Wilding G, Lippman ME, Gelmann EP. Effects of steroid hormones and peptide growth factors on protooncogene c-fos expression in human breast cancer cells. Cancer Res 1988;48:802-5.  Back to cited text no. 13
Kyprianou N, English HF, Davidson NE, Isaacs JT. Programmed cell death during regression of the MCF-7 human breast cancer following estrogen ablation. Cancer Res 1991;51:162-6.  Back to cited text no. 14
Planas-Silva MD, Bruggeman RD, Grenko RT, Smith JS. Overexpression of c-Myc and Bcl-2 during progression and distant metastasis of hormone-treated breast cancer. Exp Mol Pathol 2007;82:85-90.  Back to cited text no. 15
Molis TM, Spriggs LL, Jupiter Y, Hill SM. Melatonin modulation of estrogen-regulated proteins, growth factors, and proto-oncogenes in human breast cancer. J Pineal Res 1995;18:93-103.  Back to cited text no. 16
van der Burg B, van Selm-Miltenburg AJ, de Laat SW, van Zoelen EJ. Direct effects of estrogen on c-fos and c-myc protooncogene expression and cellular proliferation in human breast cancer cells. Mol Cell Endocrinol 1989;64:223-8.  Back to cited text no. 17
Hodges LC, Cook JD, Lobenhofer EK, Li L, Bennett L, Bushel PR, et al. Tamoxifen functions as a molecular agonist inducing cell cycle-associated genes in breast cancer cells. Mol Cancer Res 2003;1:300-11.  Back to cited text no. 18
Wang YH, Liu S, Zhang G, Zhou CQ, Zhu HX, Zhou XB, et al. Knockdown of c-Myc expression by RNAi inhibits MCF-7 breast tumor cells growth in vitro and in vivo. Breast Cancer Res 2005;7:R220-8.  Back to cited text no. 19
Watson PH, Pon RT, Shiu RP. Inhibition of c-myc expression by phosphorothioate antisense oligonucleotide identifies a critical role for c-myc in the growth of human breast cancer. Cancer Res 1991;51:3996-4000.  Back to cited text no. 20
Shi R, Peng H, Yuan X, Zhang X, Zhang Y, Fan D, et al. Down-regulation of c-fos by shRNA sensitizes adriamycin-resistant MCF-7/ADR cells to chemotherapeutic agents via P-glycoprotein inhibition and apoptosis augmentation. J Cell Biochem 2013;114:1890-900.  Back to cited text no. 21
Nezhad Koohi TK. Impact of Teicoplanin on Chromosome Aberration in CHO Cell Line First International and 13th National Congress of Genetics; Iran, Tehran; 2014.  Back to cited text no. 22