Abstract
In this study, the effect of peptides HL-7 and HL-10 was examined on human breast cancer cells (MCF-7 cell line) in the presence and absence of H2O2 and the results were compared with glutathione (GSH) served as a positive control. The results showed that the peptides showed dose-dependent cytotoxicity (P < 0.01). Additionally, enzyme activity measurements were performed to study the effect of the peptides on the activity of antioxidant enzymes in MCF-7 cell line. The results showed that in parallel to increase in the peptide concentration, the activity of antioxidant enzymes [catalase (CAT) and glutathione peroxidase (GPx)] was increased significantly in HL-7- and HL-10- treated cells after 24 h (P < 0.01). Also, to investigate the mechanism of action of the two peptides, the changes in the gene expression of CAT and GPx enzymes in the cells treated with different concentrations of peptide (25, 50, 75 and 100 µM) were evaluated using real-time PCR. The results showed that the mRNA levels of antioxidant enzymes were increased in a dose-dependent manner (P < 0.01). The increase in the activity and gene expression of the enzymes in response to HL-7 peptide was higher than HL-10 and GSH peptides. The two peptides, HL-7, and HL-10 seem to act as antioxidant agents by enhancing the gene expression and activity of antioxidant enzymes.
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References
Al-Asmari AKH, Islam M, Al-Zahrani A (2016) In vitro analysis of the anticancer properties of scorpion venom in colorectal and breast cancer cell lines. Oncol Lett 11:1256–1262. https://doi.org/10.3892/ol.2015.4036
Ali MM, Mahmoud AE, Rashad AE (2011) Inhibition of human MCF-7 breast cancer growth by free radicals enhancement of ploycondended thionopyrimidine derivatives. Asian J Pharm Clin Res 4:118–122
Asoodeh A, Haghparast A, Kashef R, Chamani J (2013) Pro-inflammatory cytokin responses of A549 epithelial cells to antimicrobial peptide brevinin-2R. Int J Pept Res Ther 19:157–162. https://doi.org/10.1007/s10989-012-9328-6
Chen HM, Muramoto K, Yamauchi F, Fujimoto K, Nokihara K (1998) Antioxidative properties of histidine-containing peptides designed from peptide fragments found in the digests of a soybean protein. J Agric Food Chem 46:49–53. https://doi.org/10.1021/jf970649w
Di Bernardini R, Harnedy P, Bolton D, Kerry J, O’Neill E, Mullen AM, Hayes M (2011) Antioxidant and antimicrobial peptidic hydrolysates from muscle protein sources and by-products. Food Chem 124: 1296–1307. https://doi.org/10.1016/j.foodchem.2010.07.004
Ganapathy E, Su F, Meriwether D, Devarajan A, Grijalva V, Gao F, Chattopadhyay A, Anantharamaiah G, Navab M, Fogelman AM (2012) D-4F, an apoA-I mimetic peptide, inhibits proliferationand tumorigenicity of epithelial ovarian cancer cells by upregulatingthe antioxidant enzyme MnSOD. Int J Cancer 130:1071–1081. https://doi.org/10.1002/ijc.26079
Halliwell B (1989) Oxidants and the central nervous system: some fundamental questions. Is oxidant damage relevant to Parkinson’s disease, Alzheimer’s disease, traumatic injury or stroke? Acta Neurol Scandinavica 80:23–33. https://doi.org/10.1111/j.1600-0404.1989.tb01779.x
Heinen TE, da Veiga A (2011) Arthropod venoms and cancer. Toxicon 57:497–511. https://doi.org/10.1016/j.toxicon.2011.01.002
Homayouni-Tabrizi M, Shabestarin H, Asoodeh A, Soltani M (2016) Identification of two novel antioxidant peptides from camel milk using digestive proteases: impact on expression gene of superoxide dismutase (SOD) in hepatocellular carcinoma cell line. Int J Pept Res Ther 22:187–195. https://doi.org/10.1007/s10989-015-9497-1
Jeon SH, Park J-H, Chang S-G (2007) Expression of antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) in human bladder cancer. Korean J Urol 48:921–926. https://doi.org/10.4111/kju.2007.48.9.921
Khan MA, Tania M, Zhang D-z, Chen H-c (2010) Antioxidant enzymes and cancer. Chin J Cancer Res 22: 67–92. https://doi.org/10.1007/s11670-010-0087-7
Li YH, Jiang B, Zhang T, Mu WM, Liu J (2008) Antioxidant and free radical scavenging activities of chickpea protein hydrolysate (CPH). Food Chem 106:444–450. https://doi.org/10.1016/j.foodchem.2007.04.067
Liaw KY, Lee PH, Wu FC, Tsai JS, Lin-Shiau SY (1997) Zinc, copper, and superoxide dismutase in hepatocellular carcinoma. Am J Gastroenterol 92:2260–2263
Mendis E, Rajapakse N, Byun HG, Kim SK (2005) Investigation of jumbo squid (Dosidicus gigas) skin gelatin peptides for their in vitro antioxidant effects. Life Sci 77:2166–2178. https://doi.org/10.1016/j.lfs.2005.03.016
Nazeer RA, Sampath Kumar NS, Jai Ganesh R (2012) In vitro and in vivo studies on the antioxidant activity of fish peptide isolated from the croaker (Otolithes ruber) muscle protein hydrolysate. Peptides 35:261–268. https://doi.org/10.1016/j.peptides.2012.03.028
Park PJ, Jung WK, Nam KS, Shahidi F, Kim SK (2001) Purification and characterization of antioxidative peptides from protein hydrolysate of lecithin-free egg yolk. J Am Oil Chem Soc 78:651–656. https://doi.org/10.1007/s11746-001-0321-0
Perez Espitia PJ, de Fátima Ferreira Soares N, dos Reis Coimbra JS, de Andrade NJ, Souza Cruz R, Alves Medeiros EA (2012) Bioactive peptides: synthesis, properties, and applications in the packaging and preservation of food. Compr Rev Food Sci Food Saf 11:187–204. https://doi.org/10.1111/j.1541-4337.2011.00179.x
Sarmadi BH, Ismail A (2010) Antioxidative peptides from food proteins: a review. Peptides 3:1949–1956. https://doi.org/10.1016/j.peptides.2010.06.020
Sarzaeem A, Zare-Mirakabadi A, Moradhaseli S, Morovvati H, Lotfi M (2012) Cytotoxic effect of ICD-85 (venom-derived peptides) on hela cancer cell line and normal LK cells using MTT assay. Arch Iran Med 15:696–701
Setayesh-Mehr Z, Asoodeh A (2018) Biochemical characterization of HL-7 and HL-10 peptides identified from scorpion venom of Hemiscorpius lepturus. Int J Pept Res Ther 24:421–430. https://doi.org/10.1007/s10989-017-9625-1
Shafaq N (2012) An overview of oxidative stress and antioxidant defensive system. Open Access Sci Rep 1:1–9. https://doi.org/10.4172/scientificreports.413
Shahbazzadeh D, Srairi-Abid N, Feng W, Ram N, Borchani L, Ronjat M, Akbari A, Pessah IN, DeWaard M, El Ayeb M (2007) Hemicalcin, a new toxin from the Iranian scorpion Hemiscorpius lepturus which is active on ryanodinesensitive Ca2+ channels. Biochem J 404:89–96. https://doi.org/10.1042/BJ20061404
Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistic, 2014. CA. 64:9–29.https://doi.org/10.3322/caac.21208
Soroceanu L, Manning TJ Jr, Sontheimer H (1999) Modulation of glioma cell migration and invasion using Cl and K ion channel blockers. J Neurosci 19:5942–5954. https://doi.org/10.1523/JNEUROSCI.19-14-05942
Srairi-Abid N, Shahbazzadeh D, Chatti I, Mlayah-Bellalouna S, Mejdoub H, Borchani L, Benkhalifa R, Akbari A, El Ayeb M (2008) Hemitoxin, the first potassium channel toxin from the venom of the Iranian scorpion Hemiscorpius lepturus. FEBS J 275:4641–4650. https://doi.org/10.1111/j.1742-4658.2008.06607.x
Taghavi A, Fazeli Z, Vahedi M, Baghestani AR, Pourhoseingholi A, Barzegar F, Pourhoseingholi MA (2012) Increased trend of breast cancer morality in Iran. Asian Pac J Cancer Prev 13:367–370. https://doi.org/10.7314/APJCP.2012.13.1.367
Timur M, Akbas SH, Ozben T (2005) The effect of Topotecan on oxidative stress in MCF-7 human breast cancer cell line. Acta Biochim Pol 52:897
Valko M, Rhodes CJ, Moncol J, Izakovic MM, Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem-Biolog Interact 160:1–40. https://doi.org/10.1016/j.cbi.2005.12.009
Weydert CJ, Cullen JJ (2010) Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nat Protoc 5:55–61. https://doi.org/10.1038/nprot.2009.197
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Zahra Setayesh-Mehr and Ahmad Asoodeh declare that they have no conflict of interest.
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Setayesh-Mehr, Z., Asoodeh, A. Inhibitory Effect of HL-7 and HL-10 Peptides on Human Breast Cancer Cells by Induction of the Expression of Antioxidant Enzymes. Int J Pept Res Ther 25, 1333–1341 (2019). https://doi.org/10.1007/s10989-018-9779-5
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DOI: https://doi.org/10.1007/s10989-018-9779-5