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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

The Anti-Breast Cancer Effects of Green-Synthesized Zinc Oxide Nanoparticles Using Carob Extracts

Author(s): Vahid Pouresmaeil*, Shaghayegh Haghighi, Asieh S. Raeisalsadati, Ali Neamati and Masoud Homayouni-Tabrizi

Volume 21, Issue 3, 2021

Published on: 21 July, 2020

Page: [316 - 326] Pages: 11

DOI: 10.2174/1871520620666200721132522

Price: $65

Abstract

Background: The use of nanoparticles synthesized by the green method to treat cancer is fairly recent. The aim of this study was to evaluate cytotoxicity, apoptotic and anti-angiogenic effects and the expression of involved genes, of Zinc Oxide Nanoparticles (ZnO-NPs) synthesized with Carob extracts on different human breast cancer cell lines.

Methods: ZnO-NPs were synthesized using the extracts of Carob and characterized with various analytical techniques. The MCF-7 and MDA-MB231 cells were treated at different times and concentrations of ZnO-NPs. The cytotoxicity, apoptosis, and anti-angiogenic effects were examined using a series of cellular assays. Expression of apoptotic genes (Bax and Bcl2) and anti-angiogenic genes, Vascular Endothelial Growth Factor (VEGF) and its Receptor (VEGF-R) in cancer cells treated with ZnO-NPs were examined with Reverse Transcriptionquantitative Polymerase Chain Reaction (RT-qPCR). The anti-oxidant activities of ZnO-NPs were evaluated by ABTS and DPPH assay.

Results: Exposure of cells to ZnO-NPs resulted in a dose-dependent loss of cell viability. The IC50 values at 24, 48, and 72 hours were 125, 62.5, and 31.2μg/ml, respectively (p<0.001). ZnO-NPs treated cells showed, in fluorescent microscopy, that ZnO-NPs are able to upregulate apoptosis and RT-qPCR revealed the upregulation of Bax (p<0.001) and downregulation of Bcl-2 (p<0.05). ZnO-NPs increased VEGF gene expression while decreasing VEGF-R (p<0.001). The anti-oxidant effects of ZnO-NPs were higher than the control group and were dose-dependent (p<0.001).

Conclusion: ZnO-NPs synthetized using Carob extract have the ability to eliminate breast cancer cells and inhibit angiogenesis, therefore, they could be used as an anticancer agent.

Keywords: Zinc oxide nanoparticle, breast cancer, cytotoxicity, apoptosis, anti-angiogenic effect, anti-oxidant effect.

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[1]
Torre, A.; Huchon, C.; Bussieres, L.; Machevin, E.; Camus, E.; Fauconnier, A. Immediate versus delayed medical treatment for first-trimester miscarriage: A randomized trial. Am. J. Obstet. Gynecol., 2012, 206(3), 215.
[http://dx.doi.org/10.1016/j.ajog.2011.12.009]
[2]
Tao, Z.; Shi, A.; Lu, C.; Song, T.; Zhang, Z.; Zhao, J. Breast cancer: Epidemiology and etiology. Cell Biochem. Biophys., 2015, 72(2), 333-338.
[http://dx.doi.org/10.1007/s12013-014-0459-6] [PMID: 25543329]
[3]
Pusztai, L.; Karn, T.; Safonov, A.; Abu-Khalaf, M.M.; Bianchini, G. New strategies in breast cancer: Immunotherapy. Clin. Cancer Res., 2016, 22(9), 2105-2110.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-1315] [PMID: 26867935]
[4]
Nishida, N.; Yano, H.; Nishida, T.; Kamura, T.; Kojiro, M. Angiogenesis in cancer. Vasc. Health Risk Manag., 2006, 2(3), 213-219.
[http://dx.doi.org/10.2147/vhrm.2006.2.3.213] [PMID: 17326328]
[5]
Dameron, K.M.; Volpert, O.V.; Tainsky, M.A.; Bouck, N. Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1. Science, 1994, 265(5178), 1582-1584.
[http://dx.doi.org/10.1126/science.7521539] [PMID: 7521539]
[6]
Bielenberg, D.R.; D’Amore, P.A. Judah Folkman’s contribution to the inhibition of angiogenesis. Lymphat. Res. Biol., 2008, 6(3-4), 203-207.
[http://dx.doi.org/10.1089/lrb.2008.1016] [PMID: 19093793]
[7]
Brem, H.; Folkman, J. Inhibition of tumor angiogenesis mediated by cartilage. J. Exp. Med., 1975, 141(2), 427-439.
[http://dx.doi.org/10.1084/jem.141.2.427] [PMID: 1113064]
[8]
Fox, S.B.; Gasparini, G.; Harris, A.L. Angiogenesis: Pathological, prognostic, and growth-factor pathways and their link to trial design and anticancer drugs. Lancet Oncol., 2001, 2(5), 278-289.
[http://dx.doi.org/10.1016/S1470-2045(00)00323-5] [PMID: 11905783]
[9]
Kossatz, S.; Grandke, J.; Couleaud, P.; Latorre, A.; Aires, A.; Crosbie-Staunton, K.; Ludwig, R.; Dähring, H.; Ettelt, V.; Lazaro-Carrillo, A.; Calero, M.; Sader, M.; Courty, J.; Volkov, Y.; Prina-Mello, A.; Villanueva, A.; Somoza, Á.; Cortajarena, A.L.; Miranda, R.; Hilger, I. Efficient treatment of breast cancer xenografts with multifunctionalized iron oxide nanoparticles combining magnetic hyperthermia and anti-cancer drug delivery. Breast Cancer Res., 2015, 17(1), 66.
[http://dx.doi.org/10.1186/s13058-015-0576-1] [PMID: 25968050]
[10]
Katiyar, S.S.; Muntimadugu, E.; Rafeeqi, T.A.; Domb, A.J.; Khan, W. Co-delivery of rapamycin- and piperine-loaded polymeric nanoparticles for breast cancer treatment. Drug Deliv., 2016, 23(7), 2608-2616.
[PMID: 26036652]
[11]
Vogel, C.L.; Cobleigh, M.A.; Tripathy, D.; Gutheil, J.C.; Harris, L.N.; Fehrenbacher, L.; Slamon, D.J.; Murphy, M.; Novotny, W.F.; Burchmore, M.; Shak, S.; Stewart, S.J.; Press, M. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J. Clin. Oncol., 2002, 20(3), 719-726.
[http://dx.doi.org/10.1200/JCO.2002.20.3.719] [PMID: 11821453]
[12]
Slamon, D.J.; Leyland-Jones, B.; Shak, S.; Fuchs, H.; Paton, V.; Bajamonde, A.; Fleming, T.; Eiermann, W.; Wolter, J.; Pegram, M.; Baselga, J.; Norton, L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med., 2001, 344(11), 783-792.
[http://dx.doi.org/10.1056/NEJM200103153441101] [PMID: 11248153]
[13]
Abbasalipourkabir, R.; Salehzadeh, A.; Abdullah, R. Cytotoxicity effect of solid lipid nanoparticles on human breast cancer cell lines. Biotechnology (Faisalabad), 2011, 10(6), 528-533.
[http://dx.doi.org/10.3923/biotech.2011.528.533]
[14]
Salehzadeh, R.; Abdullah, R. Solid lipid nanoparticles as new drug delivery system. Int. J. Biotechnol. Mol. Biol. Res., 2011, 2(13), 252-261.
[15]
Shenoy, D.B.; Amiji, M.M. Poly(ethylene oxide)-modified poly(epsilon-caprolactone) nanoparticles for targeted delivery of tamoxifen in breast cancer. Int. J. Pharm., 2005, 293(1-2), 261-270.
[http://dx.doi.org/10.1016/j.ijpharm.2004.12.010] [PMID: 15778064]
[16]
Mirzaei, H.; Darroudi, M. Zinc oxide nanoparticles: Biological synthesis and biomedical applications. Ceram. Int., 2017, 43(1), 907-914.
[http://dx.doi.org/10.1016/j.ceramint.2016.10.051]
[17]
Sanaeimehr, Z.; Javadi, I.; Namvar, F. Antiangiogenic and antiapoptotic effects of green-synthesized zinc oxide nanoparticles using Sargassum muticum algae extraction. Cancer Nanotechnol., 2018, 9(1), 3.
[http://dx.doi.org/10.1186/s12645-018-0037-5] [PMID: 29628994]
[18]
Jiang, J.; Pi, J.; Cai, J. The advancing of zinc oxide nanoparticles for biomedical applications. Bioinorg. Chem. Appl., 2018, 2018Article ID 1062562
[http://dx.doi.org/10.1155/2018/1062562]
[19]
Vandebriel, R.J.; De Jong, W.H. A review of mammalian toxicity of ZnO nanoparticles. Nanotechnol. Sci. Appl., 2012, 5, 61-71.
[http://dx.doi.org/10.2147/NSA.S23932] [PMID: 24198497]
[20]
Iravani, S. Green synthesis of metal nanoparticles using plants. Green Chem., 2011, 13(10), 2638-2650.
[http://dx.doi.org/10.1039/c1gc15386b]
[21]
Sangeetha, G.; Rajeshwari, S.; Venckatesh, R. Green synthesis of zinc oxide nanoparticles by Aloe Barbadensis Miller leaf extract: Structure and optical properties. Mater. Res. Bull., 2011, 46(12), 2560-2566.
[http://dx.doi.org/10.1016/j.materresbull.2011.07.046]
[22]
Salam, H.A.; Sivaraj, R.; Venckatesh, R. Green synthesis and characterization of zinc oxide nanoparticles from Ocimum basilicum L. var. purpurascens Benth.-Lamiaceae leaf extract. Mater. Lett., 2014, 131, 16-18.
[http://dx.doi.org/10.1016/j.matlet.2014.05.033]
[23]
Senthilkumar, S.; Sivakumar, T. Green tea (Camellia sinensis) mediated synthesis of Zinc Oxide (ZnO) nanoparticles and studies on their antimicrobial activities. Int. J. Pharm. Pharm. Sci., 2014, 6(6), 461-465.
[24]
Avallone, R.; Plessi, M.; Baraldi, M.; Monzani, A. Determination of chemical composition of carob (Ceratonia siliqua): Protein, fat, carbohydrates, and tannins. J. Food Compos. Anal., 1997, 10(2), 166-172.
[http://dx.doi.org/10.1006/jfca.1997.0528]
[25]
Baraldi, M. Extract of Ceratonia siliqua leaves and pods containing polyphenols with antioxidant and antitumor activities. WO Patent 2003033006A8, 2009.
[26]
Ayaz, F.A.; Torun, H.; Ayaz, S.; Correia, P.J.; Alaiz, M.; Sanz, C.; Gruz, J.; Strnad, M. Determination of chemical composition of anatolian carob pod (Ceratonia siliqua L.): Sugars, amino and organic acids, minerals and phenolic compounds. J. Food Qual., 2007, 30(6), 1040-1055.
[http://dx.doi.org/10.1111/j.1745-4557.2007.00176.x]
[27]
Custodio, L.; Fernandes, E.; Escapa, A.L.; Lopez-Aviles, S.; Fajardo, A.; Aligue, R.; Albericio, F.; Romano, A. Antioxidant activity and in vitro inhibition of tumor cell growth by leaf extracts from the carob tree (Ceratonia siliqua). Pharm. Biol., 2009, 47(8), 721-728.
[http://dx.doi.org/10.1080/13880200902936891]
[28]
Yedurkar, S.; Maurya, C.; Mahanwar, P. Biosynthesis of zinc oxide nanoparticles using Ixora coccinea leaf extract - a green approach. Open J. Synthes. Theory Appl., 2016, 5(01), 1.
[http://dx.doi.org/10.4236/ojsta.2016.51001]
[29]
Thirumavalavan, M.; Huang, K-L.; Lee, J-F. Preparation and morphology studies of nano zinc oxide obtained using native and modified chitosans. Materials (Basel), 2013, 6(9), 4198-4212.
[http://dx.doi.org/10.3390/ma6094198] [PMID: 28788326]
[30]
Wahab, R.; Siddiqui, M.A.; Saquib, Q.; Dwivedi, S.; Ahmad, J.; Musarrat, J.; Al-Khedhairy, A.A.; Shin, H-S. ZnO nanoparticles induced oxidative stress and apoptosis in HepG2 and MCF-7 cancer cells and their antibacterial activity. Colloids Surf. B Biointerfaces, 2014, 117, 267-276.
[http://dx.doi.org/10.1016/j.colsurfb.2014.02.038] [PMID: 24657613]
[31]
Vimala, K.; Sundarraj, S.; Paulpandi, M.; Vengatesan, S.; Kannan, S. Green synthesized doxorubicin loaded zinc oxide nanoparticles regulates the Bax and Bcl-2 expression in breast and colon carcinoma. Process Biochem., 2014, 49(1), 160-172.
[http://dx.doi.org/10.1016/j.procbio.2013.10.007]
[32]
Akhtar, M.J.; Ahamed, M.; Kumar, S.; Khan, M.M.; Ahmad, J.; Alrokayan, S.A. Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species. Int. J. Nanomedicine, 2012, 7, 845-857.
[PMID: 22393286]
[33]
Alarifi, S.; Ali, D.; Alkahtani, S.; Verma, A.; Ahamed, M.; Ahmed, M.; Alhadlaq, H.A. Induction of oxidative stress, DNA damage, and apoptosis in a malignant human skin melanoma cell line after exposure to zinc oxide nanoparticles. Int. J. Nanomedicine, 2013, 8, 983-993.
[PMID: 23493450]
[34]
Fakhari, S.; Jamzad, M.; Kabiri Fard, H. Green synthesis of zinc oxide nanoparticles: A comparison. Green Chem. Lett. Rev., 2019, 12(1), 19-24.
[http://dx.doi.org/10.1080/17518253.2018.1547925]
[35]
Hajiashrafi, S.; Motakef-Kazemi, N. Green synthesis of zinc oxide nanoparticles using parsley extract. Nanomed. Res. J., 2018, 3(1), 44-50.
[36]
Ezealisiji, K.M.; Siwe-Noundou, X.; Maduelosi, B.; Nwachukwu, N.; Krause, R.W.M. Green synthesis of zinc oxide nanoparticles using Solanum torvum (L) leaf extract and evaluation of the toxicological profile of the ZnO nanoparticles-hydrogel composite in Wistar albino rats. Int. Nano Lett., 2019, 9(2), 99-107.
[http://dx.doi.org/10.1007/s40089-018-0263-1]
[37]
Moldovan, B.; Sincari, V.; Perde-Schrepler, M.; David, L. Biosynthesis of silver nanoparticles using Ligustrum ovalifolium fruits and their cytotoxic effects. Nanomaterials (Basel), 2018, 8(8), 627.
[http://dx.doi.org/10.3390/nano8080627] [PMID: 30126197]
[38]
Jain, S.; Mehata, M.S. Medicinal plant leaf extract and pure flavonoid mediated green synthesis of silver nanoparticles and their enhanced antibacterial property. Sci. Rep., 2017, 7(1), 15867.
[http://dx.doi.org/10.1038/s41598-017-15724-8] [PMID: 29158537]
[39]
Malaikozhundan, B.; Vaseeharan, B.; Vijayakumar, S.; Pandiselvi, K.; Kalanjiam, M.A.R.; Murugan, K.; Benelli, G. Biological therapeutics of Pongamia pinnata coated zinc oxide nanoparticles against clinically important pathogenic bacteria, fungi and MCF-7 breast cancer cells. Microb. Pathog., 2017, 104, 268-277.
[http://dx.doi.org/10.1016/j.micpath.2017.01.029] [PMID: 28115262]
[40]
Custodio, L.; Fernandes, E.; Escapa, A.; Lopez-Aviles, S.; Fajardo, A.; Aligue, R.; Albericio, F.; Romano, A. Antiproliferative and apoptotic activities of extracts from carob tree (Ceratonia siliqua L.) in MDA-MB-231 human breast cancer cells. Planta Med., 2008, 74(09), PA48.
[http://dx.doi.org/10.1055/s-0028-1084046]
[41]
Dhamodarana, M.; Kavithab, S. Anticancer activity of zinc nanoparticles made using terpenoids from aqueous leaf extract of Andrographis paniculata. Int. J. Pharmaceut. Sci. Nanotechnol., 2015, 8(4), 3018-3023.
[42]
Pandurangan, M.; Kim, D.H. In vitro toxicity of zinc oxide nanoparticles: A review. J. Nanopart. Res., 2015, 17(3), 158.
[http://dx.doi.org/10.1007/s11051-015-2958-9]
[43]
Chung, I-M.; Rahuman, A.A.; Marimuthu, S.; Kirthi, A.V.; Anbarasan, K.; Rajakumar, G. An investigation of the cytotoxicity and caspase-mediated apoptotic effect of green synthesized zinc oxide nanoparticles using Eclipta prostrata on human liver carcinoma cells. Nanomaterials (Basel), 2015, 5(3), 1317-1330.
[http://dx.doi.org/10.3390/nano5031317] [PMID: 28347066]
[44]
Ventura, A.; Kirsch, D.G.; McLaughlin, M.E.; Tuveson, D.A.; Grimm, J.; Lintault, L.; Newman, J.; Reczek, E.E.; Weissleder, R.; Jacks, T. Restoration of p53 function leads to tumour regression in vivo. Nature, 2007, 445(7128), 661-665.
[http://dx.doi.org/10.1038/nature05541] [PMID: 17251932]
[45]
Choi, H.S.; Ashitate, Y.; Lee, J.H.; Kim, S.H.; Matsui, A.; Insin, N.; Bawendi, M.G.; Semmler-Behnke, M.; Frangioni, J.V.; Tsuda, A. Rapid translocation of nanoparticles from the lung airspaces to the body. Nat. Biotechnol., 2010, 28(12), 1300-1303.
[http://dx.doi.org/10.1038/nbt.1696] [PMID: 21057497]
[46]
Gojova, A.; Guo, B.; Kota, R.S.; Rutledge, J.C.; Kennedy, I.M.; Barakat, A.I. Induction of inflammation in vascular endothelial cells by metal oxide nanoparticles: Effect of particle composition. Environ. Health Perspect., 2007, 115(3), 403-409.
[http://dx.doi.org/10.1289/ehp.8497] [PMID: 17431490]
[47]
Wei, L-H.; Kuo, M-L.; Chen, C-A.; Chou, C-H.; Lai, K-B.; Lee, C-N.; Hsieh, C-Y. Interleukin-6 promotes cervical tumor growth by VEGF-dependent angiogenesis via a STAT3 pathway. Oncogene, 2003, 22(10), 1517-1527.
[http://dx.doi.org/10.1038/sj.onc.1206226] [PMID: 12629515]
[48]
Tada-Oikawa, S.; Ichihara, G.; Suzuki, Y.; Izuoka, K.; Wu, W.; Yamada, Y.; Mishima, T.; Ichihara, S. Zn(II) released from zinc oxide nano/micro particles suppresses vasculogenesis in human endothelial colony-forming cells. Toxicol. Rep., 2015, 2, 692-701.
[http://dx.doi.org/10.1016/j.toxrep.2015.04.003] [PMID: 28962405]
[49]
Rehana, D.; Mahendiran, D.; Kumar, R.S.; Rahiman, A.K. In vitro antioxidant and antidiabetic activities of zinc oxide nanoparticles synthesized using different plant extracts. Bioprocess Biosyst. Eng., 2017, 40(6), 943-957.
[http://dx.doi.org/10.1007/s00449-017-1758-2] [PMID: 28361361]
[50]
Nagajyothi, P.C.; Cha, S.J.; Yang, I.J.; Sreekanth, T.V.; Kim, K.J.; Shin, H.M. Antioxidant and anti-inflammatory activities of zinc oxide nanoparticles synthesized using Polygala tenuifolia root extract. J. Photochem. Photobiol. B, 2015, 146, 10-17.
[http://dx.doi.org/10.1016/j.jphotobiol.2015.02.008] [PMID: 25777265]
[51]
Mahendiran, D.; Subash, G.; Selvan, D.A.; Rehana, D.; Kumar, R.S.; Rahiman, A.K. Biosynthesis of zinc oxide nanoparticles using plant extracts of aloe vera and Hibiscus sabdariffa: Phytochemical, antibacterial, antioxidant and anti-proliferative studies. Bionanoscience, 2017, 7(3), 530-545.
[http://dx.doi.org/10.1007/s12668-017-0418-y]
[52]
Vamanu, C.I.; Cimpan, M.R.; Hol, P.J.; Sornes, S.; Lie, S.A.; Gjerdet, N.R. Induction of cell death by TiO2 nanoparticles: Studies on a human monoblastoid cell line. Toxicol. In Vitro, 2008, 22(7), 1689-1696.
[http://dx.doi.org/10.1016/j.tiv.2008.07.002] [PMID: 18672048]
[53]
Baharara, J.; Namvar, F.; Ramezani, T.; Hosseini, N.; Mohamad, R. Green synthesis of silver nanoparticles using Achillea biebersteinii flower extract and its anti-angiogenic properties in the rat aortic ring model. Molecules, 2014, 19(4), 4624-4634.
[http://dx.doi.org/10.3390/molecules19044624] [PMID: 24739926]
[54]
Gurunathan, S.; Lee, K.J.; Kalishwaralal, K.; Sheikpranbabu, S.; Vaidyanathan, R.; Eom, S.H. Antiangiogenic properties of silver nanoparticles. Biomaterials, 2009, 30(31), 6341-6350.
[http://dx.doi.org/10.1016/j.biomaterials.2009.08.008] [PMID: 19698986]

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