Abstract
Cupric oxide nanoparticles (CuO NPs) were phytofabricated utilizing leaf extract of Simarouba glauca and aerial extract of Celastrus paniculatus and are considered to hold excellent anticancer capability. Synthesized CuO NPs were characterized for their morphology, crystallinity, and structure. The presence of functional groups of phytochemicals on synthesized nanoparticles was validated by Fourier transform infrared spectroscopy (FTIR) analysis. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) examination reveal the uniform distribution of particles and the average particle size is 35 nm. The anticancer activities on MCF-7 and HT-29 cell lines revealed that CuO NPs synthesized using leaf extract of S. glauca (CuO-SG) induced cell death with half-maximal inhibitory concentration (IC50) value of 107.56 µg/mL and 208.57 µg/mL, while CuO NPs synthesized using the aerial extract of C. paniculatus (CuO-CP) indicated IC50 values of 97.39 µg/mL and 205.11 µg/mL, respectively. To be more precise for anti-cancerous effect, the molecular mechanism was examined in MCF-7 cell line treated with CuO-CP NPs by cell cycle analysis that depicted 75.28% of cell arrest in Sub G0/G1 phase and 71.29% of cells were gated in the late apoptotic phase of Annexin V and propidium iodide (PI) compared to control cells. The present work reports in vivo antitumor studies of CuO-CP NPs against Ehrlich ascites carcinoma (EAC) bearing C57 mice for the first time and was examined by variations in growth parameters, biochemical assays, hematological profile, and histopathological analysis. CuO-CP NPs could eliminate oxidants like lactoperoxidase and myeloperoxidase, stimulate reduced glutathione, restore the hematological profile and increase the life span of tumor-bearing mice treated by them in comparison with control.
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References
Abramov OV, Gedanken A, Koltypin Y et al (2009) Pilot scale sonochemical coating of nanoparticles onto textiles to produce biocidal fabrics. Surf Coatings Technol 204:718–722. https://doi.org/10.1016/j.surfcoat.2009.09.030
Ahmed M, Rana A, Dixit V (2005) Calotropis species (Ascelpediaceace)—a comprehensive review. Pharmacogn Mag 1:48–52
Alves IABS, Miranda HM, Soares LAL, Randau KP (2014) Simaroubaceae family: botany, chemical composition and biological activities. Rev Bras Farmacogn 24:481–501. https://doi.org/10.1016/j.bjp.2014.07.021
Arya A, Gupta K, Chundawat TS, Vaya D (2018) Biogenic synthesis of copper and silver nanoparticles using green alga Botryococcus braunii and its antimicrobial activity. Bioinorg Chem Appl 2018:1–9. https://doi.org/10.1155/2018/7879403
Azizian-Shermeh O, Einali A, Ghasemi A (2017) Rapid biologically one-step synthesis of stable bioactive silver nanoparticles using Osage orange (Maclura pomifera) leaf extract and their antimicrobial activities. Adv Powder Technol 28:3164–3171. https://doi.org/10.1016/j.apt.2017.10.001
Baghizadeh A, Ranjbar S, Gupta VK et al (2015) Green synthesis of silver nanoparticles using seed extract of Calendula officinalis in liquid phase. J Mol Liq 207:159–163. https://doi.org/10.1016/j.molliq.2015.03.029
Bai L, Meng Y, Khan ZA, Zhang V (2017) The synergetic effects of surface texturing and MoDDP additive applied to ball-on-disk friction subject to both flooded and starved lubrication conditions. Tribol Lett 65:163. https://doi.org/10.1007/s11249-017-0949-y
Baik N, seok, Sakai G, Miura N, Yamazoe N, (2000) Preparation of stabilized nanosized tin oxide particles by hydrothermal treatment. J Am Ceram Soc 83:2983–2987. https://doi.org/10.1111/j.1151-2916.2000.tb01670.x
Barbosa LF, Braz-Filho R, Vieira IJC (2011) Chemical constituents of plants from the genus Simaba (Simaroubaceae). Chem Biodivers 8:2163–2178. https://doi.org/10.1002/cbdv.201000323
Berra D, Laouini SE, Benhaoua B et al (2018) Green synthesis of copper oxide nanoparticles by Pheonix dactylifera L leaves extract. Dig J Nanomater Biostructures 13:1231–1238
Cheon J, Lee J, Kim J (2012) Inkjet printing using copper nanoparticles synthesized by electrolysis. Thin Solid Films 520:2639–2643. https://doi.org/10.1016/j.tsf.2011.11.021
Das D, Nath BC, Phukon P, Dolui SK (2013) Synthesis and evaluation of antioxidant and antibacterial behavior of CuO nanoparticles. Colloids Surf B Biointerfaces 101:430–433. https://doi.org/10.1016/j.colsurfb.2012.07.002
Dhanya S, Isloor AM, Shetty P, Nayak PG, Pai KSR (2013) In vivo anticancer and histopathology studies of Schiff bases on Ehrlich ascitic carcinoma cells: 1st cancer update. Arab J Chem 6:25–33. https://doi.org/10.1016/j.arabjc.2010.12.016
Dugo EB, Yedjou CG, Stevens JJ, Tchounwou PB (2017) Therapeutic potential of arsenic trioxide (ATO) in treatment of hepatocellular carcinoma: role of oxidative stress in ATO-induced apoptosis. Ann Clin Pathol 5:1101–1128
Eissa MI, El-Sherbiny MA, Ibrahim AM et al (2019) Biochemical and Histopathological studies on female and male Wistar rats fed on genetically modified soybean meals (Roundup Ready). J Basic Appl Zool 80:54. https://doi.org/10.1186/s41936-019-0114-2
El-Far M, Salah N, Essam A et al (2019) Potential anticancer activity and mechanism of action of nanoformulated curcumin in experimental Ehrlich ascites carcinoma-bearing animals. Nanomedicine 14:553–573. https://doi.org/10.2217/nnm-2018-0298
Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77. https://doi.org/10.1016/0003-9861(59)90090-6
Elsayed WM, Abdel-Gawad E-HAHA, Mesallam DIAA, El-Serafy TS (2020) The relationship between oxidative stress and acute ischemic stroke severity and functional outcome. Egypt J Neurol Psychiatry Neurosurg 56:1–6. https://doi.org/10.1186/s41983-020-00206-y
Ethiraj AS, Kang DJ (2012) Synthesis and characterization of CuO nanowires by a simple wet chemical method. Nanoscale Res Lett 7:70. https://doi.org/10.1186/1556-276X-7-70
Gopinath V, Priyadarshini S, Al-Maleki AR et al (2016) In vitro toxicity, apoptosis and antimicrobial effects of phyto-mediated copper oxide nanoparticles. RSC Adv 6:110986–110995. https://doi.org/10.1039/C6RA13871C
Harish B, Krishna V, Kumar H et al (2008a) Wound healing activity and docking of glycogen-synthase-kinase-3-β-protein with isolated triterpenoid lupeol in rats. Phytomedicine 15:763–767. https://doi.org/10.1016/j.phymed.2007.11.017
Hassanien R, Husein DZ, Al-Hakkani MF (2018) Biosynthesis of copper nanoparticles using aqueous Tilia extract: antimicrobial and anticancer activities. Heliyon 4:e01077. https://doi.org/10.1016/j.heliyon.2018.e01077
Hwa KY, Karuppaiah P, Gowthaman NSK et al (2019) Ultrasonic synthesis of CuO nanoflakes: a robust electrochemical scaffold for the sensitive detection of phenolic hazard in water and pharmaceutical samples. Ultrason Sonochem 58:104649
Karmakar I, Dolai N, Suresh Kumar RB et al (2013) Antitumor activity and antioxidant property of Curcuma caesia against Ehrlich’s ascites carcinoma bearing mice. Pharm Biol 51:753–759. https://doi.org/10.3109/13880209.2013.764538
Kiessling F, Liu Z, Gätjens J et al (2010) Advanced nanomaterials in multimodal imaging: design, functionalization, and biomedical applications. J Nanomater 2010:1–15. https://doi.org/10.1155/2010/894303
Koca FD, Demirezen Yilmaz D, Duman F, Ocsoy I (2018) Comparison of phytotoxic effects of bio-synthesised copper oxide nanoparticle and ionic copper on Elodea canadensis. Chem Ecol 34:839–853. https://doi.org/10.1080/02757540.2018.1494162
Kumar KH, Venuprasad MP, Jayashree GV et al (2015) Celastrus paniculatus Willd. mitigates t-BHP induced oxidative and apoptotic damage in C2C12 murine muscle cells. Cytotechnology 67:955–967. https://doi.org/10.1007/s10616-014-9733-0
Kumar KHK, Razack S, IN-IC, et al (2014) Phytochemical analysis and biological properties of Cyperus rotundus L. Ind Crops Prod 52:815–826. https://doi.org/10.1039/C8RA07985D
Kumar RS, Almansour AI, Arumugam N et al (2018) Highly functionalized pyrrolidine analogues: stereoselective synthesis and caspase-dependent apoptotic activity. RSC Adv 8:41226–41236
Li Y-MM, Sun S-QQ, Zhou Q et al (2004) Identification of American ginseng from different regions using FT-IR and two-dimensional correlation IR spectroscopy. Vib Spectrosc 36:227–232. https://doi.org/10.1016/j.vibspec.2003.12.009
Li Y, Liang J, Tao Z, Chen J (2008) CuO particles and plates: synthesis and gas-sensor application. Mater Res Bull 43:2380–2385. https://doi.org/10.1016/j.materresbull.2007.07.045
Mathuram TL, Ravikumar V, Reece LM et al (2016) Tideglusib induces apoptosis in human neuroblastoma IMR32 cells, provoking sub-G0/G1 accumulation and ROS generation. Environ Toxicol Pharmacol 46:194–205. https://doi.org/10.1016/j.etap.2016.07.013
Meghana S, Kabra P, Chakraborty S, Padmavathy N (2015) Understanding the pathway of antibacterial activity of copper oxide nanoparticles. RSC Adv 5:12293–12299. https://doi.org/10.1039/C4RA12163E
Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63. https://doi.org/10.1016/0022-1759(83)90303-4
Mullane KM, Kraemer R, Smith B (1985) Myeloperoxidase activity as a quantitative assessment of neutrophil infiltration into ischemie myocardium. J Pharmacol Methods 14:157–167. https://doi.org/10.1016/0160-5402(85)90029-4
Munawer U, Raghavendra VB, Ningaraju S et al (2020) Biofabrication of gold nanoparticles mediated by the endophytic Cladosporium species: photodegradation, in vitro anticancer activity and in vivo antitumor studies. Int J Pharm 588:29–41. https://doi.org/10.1016/j.ijpharm.2020.119729
Nagajyothi PC, Muthuraman P, Sreekanth TVM et al (2017) Green synthesis: in-vitro anticancer activity of copper oxide nanoparticles against human cervical carcinoma cells. Arab J Chem 10:215–225. https://doi.org/10.1016/j.arabjc.2016.01.011
Nagaonkar D, Shende S, Rai M (2015) Biosynthesis of copper nanoparticles and its effect on actively dividing cells of mitosis in Allium cepa. Biotechnol Prog 31:557–565. https://doi.org/10.1002/btpr.2040
Naika HR, Lingaraju K, Manjunath K et al (2015) Green synthesis of CuO nanoparticles using Gloriosa superba L. extract and their antibacterial activity. J Taibah Univ Sci 9:7–12. https://doi.org/10.1016/j.jtusci.2014.04.006
Namvar F, Sulaiman Rahman H, Mohammad R, Baharara J, Mahdavi M, Amini E, Stanley Chartrand M, Yeap SK, Namvar F, Rahman HS et al (2014) Cytotoxic effect of magnetic iron oxide nanoparticles synthesized via seaweed aqueous extract. Int J Nanomedicine 9:2479–2488. https://doi.org/10.2147/IJN.S59661
Nasrollahzadeh M, Sajadi SM, Maham M (2015) Tamarix gallica leaf extract mediated novel route for green synthesis of CuO nanoparticles and their application for N-arylation of nitrogen-containing heterocycles under ligand-free conditions. RSC Adv 5:40628–40635. https://doi.org/10.1039/c5ra04012d
Nethravathi PC, Kumar MAP, Suresh D et al (2015) Tinospora cordifolia mediated facile green synthesis of cupric oxide nanoparticles and their photocatalytic, antioxidant and antibacterial properties. Mater Sci Semicond Process 33:81–88. https://doi.org/10.1016/j.mssp.2015.01.034
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358. https://doi.org/10.1016/0003-2697(79)90738-3
Olayode OA, Daniyan MO, Olayiwola G (2019) Biochemical, hematological and histopathological evaluation of the toxicity potential of the leaf extract of Stachytarpheta cayennensis in rats. J Tradit Complement Med 10:544–554. https://doi.org/10.1016/j.jtcme.2019.05.001
Patil R, Prakash K, Clinical VM-I, journal of, (2010) U (2010) Hypolipidemic effect of Celastrus paniculatus in experimentally induced hypercholesterolemic wistar rats. Springer 25:405–410. https://doi.org/10.1007/s12291-010-0050-x
Rajashekaraiah R, Kumar PR, Prakash N et al (2020) Anticancer efficacy of 6-thioguanine loaded chitosan nanoparticles with or without curcumin. Int J Biol Macromol 148:704–714. https://doi.org/10.1016/j.ijbiomac.2020.01.117
Rajkumar R, Kumar EP, Sudha S, Suresh B (2007) Evaluation of anxiolytic potential of Celastrus oil in rat models of behaviour. Fitoterapia 78:120–124. https://doi.org/10.1016/j.fitote.2006.09.028
Ramamurthy N, Kannan S (2007) Fourier transform infrared spectroscopic analysis of a plant (Calotropis gigantea Linn) from an industrial village, Cuddalore dt, Tamilnadu, India. Rom J Biophys 17:269–276
Ramaswamy SVP, Narendhran S, Sivaraj R (2016) Potentiating effect of ecofriendly synthesis of copper oxide nanoparticles using brown alga: antimicrobial and anticancer activities. Bull Mater Sci 39:361–364. https://doi.org/10.1007/s12034-016-1173-3
Rao CNR (1963) Chemical applications of infrared spectroscopy. Science. Academic Press, p 1441
Ray asit, Jena S, Dash B, et al (2019) Hedychium coronarium extract arrests cell cycle progression, induces apoptosis, and impairs migration and invasion in HeLa cervical cancer cells. Cancer Manag Res 11:483. https://doi.org/10.2147/CMAR.S190004
Rehana D, Mahendiran D, Kumar RS, Rahiman AK (2017) Evaluation of antioxidant and anticancer activity of copper oxide nanoparticles synthesized using medicinally important plant extracts. Biomed Pharmacother 89:1067–1077. https://doi.org/10.1016/j.biopha.2017.02.101
Saif S, Tahir A, Asim T, et al (2016) Plant mediated green synthesis of CuO nanoparticles: comparison of toxicity of engineered and plant mediated CuO nanoparticles towards Daphnia magna. mdpi.com 6:205. doi: https://doi.org/10.3390/nano6110205
Sari LM, Subita GP, Auerkari EI (2018) Areca nut extract demonstrated apoptosis-inducing mechanism by increased caspase-3 activities on oral squamous cell carcinoma. F1000Research 7:1–34. https://doi.org/10.12688/f1000research.14856.5
Seigneuric R, Markey L, S.A. Nuyten D, et al (2010) From nanotechnology to nanomedicine: applications to cancer research. Curr Mol Med 10:640–652. https://doi.org/10.2174/156652410792630634
Sivaraj R, Rahman PKSMSM, Rajiv P et al (2014a) Biosynthesis and characterization of Acalypha indica mediated copper oxide nanoparticles and evaluation of its antimicrobial and anticancer activity. Spectrochim Acta Part A Mol Biomol Spectrosc 129:255–258. https://doi.org/10.1016/j.saa.2014.03.027
Sivaraj R, Rahman PKSMSM, Rajiv P et al (2014b) Biogenic copper oxide nanoparticles synthesis using Tabernaemontana divaricate leaf extract and its antibacterial activity against urinary tract pathogen. Spectrochim Acta Part A Mol Biomol Spectrosc 133:178–181. https://doi.org/10.1016/j.saa.2014.05.048
Suárez-Cerda J, Espinoza-Gómez H, Alonso-Núñez G et al (2017) A green synthesis of copper nanoparticles using native cyclodextrins as stabilizing agents. J Saudi Chem Soc 21:341–348. https://doi.org/10.1016/j.jscs.2016.10.005
Sulaiman GM, Tawfeeq AT, Jaaffer MD (2018) Biogenic synthesis of copper oxide nanoparticles using olea europaea leaf extract and evaluation of their toxicity activities: an in vivo and in vitro study. Biotechnol Prog 34:218–230. https://doi.org/10.1002/btpr.2568
Suresh D, Nethravathi PC, Udayabhanu, et al (2015a) Green synthesis of multifunctional zinc oxide (ZnO) nanoparticles using Cassia fistula plant extract and their photodegradative, antioxidant and antibacterial activities. Mater Sci Semicond Process 31:446–454. https://doi.org/10.1016/j.mssp.2014.12.023
Suresh D, Udayabhanu NPC et al (2015b) EGCG assisted green synthesis of ZnO nanopowders: photodegradative, antimicrobial and antioxidant activities. Spectrochim Acta Part A Mol Biomol Spectrosc 136:1467–1474. https://doi.org/10.1016/j.saa.2014.10.038
Suresh Y, Annapurna S, Bhikshamaiah G, Singh AK (2016) Green luminescent copper nanoparticles. Mater Sci Eng C 149:12187. https://doi.org/10.1088/1757-899X/149/1/012187
Tarasov S, Kolubaev A, Belyaev S et al (2002) Study of friction reduction by nanocopper additives to motor oil. Wear 252:63–69. https://doi.org/10.1016/S0043-1648(01)00860-2
Thenmozhi T (2020) Functionalization of iron oxide nanoparticles with clove extract to induce apoptosis in MCF-7 breast cancer cells. 3 Biotech 10:82. https://doi.org/10.1007/s13205-020-2088-7
Thylur RP, Senthivinayagam S, Campbell EM et al (2011) Mixed lineage kinase 3 modulates β-catenin signaling in cancer cells. J Biol Chem 286:37470–37482. https://doi.org/10.1074/jbc.m111.298943
Uddandrao VVS, Parim B, Nivedha PR et al (2019) Anticancer activity of pomegranate extract: effect on hematological and antioxidant profile against ehrlich-ascites-carcinoma in Swiss albino mice. Orient Pharm Exp Med 19:243–250
Verma N, Kumar N (2019) Synthesis and biomedical applications of copper oxide nanoparticles: an expanding horizon. ACS Biomater Sci Eng 5:1170–1188. https://doi.org/10.1021/acsbiomaterials.8b01092
Vishveshvar K, Aravind Krishnan MV, Haribabu K et al (2018) Green synthesis of copper oxide nanoparticles using Ixiro coccinea plant leaves and its characterization. Bionanoscience 8:554–558. https://doi.org/10.1007/s12668-018-0508-5
Wadhwa R, Aggarwal T, Thapliyal N et al (2019) Red blood cells as an efficient in vitro model for evaluating the efficacy of metallic nanoparticles. 3 Biotech 9:279. https://doi.org/10.1007/s13205-019-1807-4
Wang X, Wang L, Fu Y et al (2013) Promising effects on ameliorating mitochondrial function and enhancing Akt signaling in SH-SY5Y cells by (M)-bicelaphanol A, a novel dimeric podocarpane type. Phytomedicine 20:1064–1070. https://doi.org/10.1016/j.phymed.2013.04.017
Weng JJ-R, Yen M-HM, Lin W-Y et al (2013) Cytotoxic constituents from Celastrus paniculatus induce apoptosis and autophagy in breast cancer cells. Phytochemistry 94:211–219. https://doi.org/10.1016/j.phytochem.2013.05.022
WHO 2018 (2018) Latest global cancer data: Cancer burden rises to 18.1 million new cases and 9.6 million cancer deaths in 2018
Xie W, Zhang Z, Liao L et al (2020) Green chemical mechanical polishing of sapphire wafers using a novel slurry. Nanoscale 12:22518–22526. https://doi.org/10.1039/D0NR04705H
Ye T, Guiwen Z, Weiping Z, Shangda X (1997) Combustion synthesis and photoluminescence of nanocrystalline Y2O3: Eu phosphors. Mater Res Bull 32:501–506. https://doi.org/10.1016/S0025-5408(97)00007-X
Zhang Z, Cui J, Wang B et al (2017) A novel approach of mechanical chemical grinding. J Alloys Compd 726:514–524. https://doi.org/10.1016/j.jallcom.2017.08.024
Zhang Z, Cui J, Zhang J et al (2019) Environment friendly chemical mechanical polishing of copper. Appl Surf Sci 467–468:5–11. https://doi.org/10.1016/j.apsusc.2018.10.133
Zhang Z, Guo D, Wang B et al (2015) A novel approach of high speed scratching on silicon wafers at nanoscale depths of cut. Sci Rep 5:16395. https://doi.org/10.1038/srep16395
Zhang Z, Huo F, Zhang X, Guo D (2012) Fabrication and size prediction of crystalline nanoparticles of silicon induced by nanogrinding with ultrafine diamond grits. Scr Mater 67:657–660. https://doi.org/10.1016/j.scriptamat.2012.07.016
Zhang Z, Huo Y, Guo D (2013) A model for nanogrinding based on direct evidence of ground chips of silicon wafers. Sci China Technol Sci 56:2099–2108. https://doi.org/10.1007/s11431-013-5286-2
Zhang Z, Liao L, Wang X et al (2020) Development of a novel chemical mechanical polishing slurry and its polishing mechanisms on a nickel alloy. Appl Surf Sci 506:144670. https://doi.org/10.1016/j.apsusc.2019.144670
Zhang Z, Liu J, Hu W et al (2021) Chemical mechanical polishing for sapphire wafers using a developed slurry. J Manuf Process 62:762–771. https://doi.org/10.1016/j.jmapro.2021.01.004
Acknowledgments
The authors are thankful to Vision Group on Science and Technology, Department of IT, BT and S&T, Government of Karnataka for financial assistance to the Department of Nanotechnology under the K-FIST scheme. Authors are also grateful to UGC for the BSR faculty fellowship to KSR (grant no.F.18-1/2011 (BSR)), Institute of Excellence (IOE) for spectral support at the University of Mysore, Manasagangotri, Mysuru-570006, India. Authors acknowledge the support extended by the expert Plant Taxonomist, Dr. K. Ravikumar, Professor, TDU & Asst. Director for FRLH Herbarium and Raw Drug Repository, FRLHT, Bengaluru for guidance in identifying the plant materials and providing the herbarium certificate for the same and Dr. Takashi Morii, Dr. Arivazhagan Rajendran, and Dr. Shun Nakano, Institute of Advanced Energy, Kyoto University, Uji, Japan, for providing facility to perform TEM analysis.
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Giridasappa, A., Rangappa, D., Shanubhoganahalli Maheswarappa, G. et al. Phytofabrication of cupric oxide nanoparticles using Simarouba glauca and Celastrus paniculatus extracts and their enhanced apoptotic inducing and anticancer effects. Appl Nanosci 11, 1393–1409 (2021). https://doi.org/10.1007/s13204-021-01753-3
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DOI: https://doi.org/10.1007/s13204-021-01753-3