Background: Development of novel strategies to kill cancer by sparing normal cells is of utmost importance. Apart from their known antimicrobial activity, only limited information has been recorded regarding the antitumor potential of biocompatible silver oxide nanoparticles (AgONPs). There is a need to evaluate the anticancer potential of biocompatible AgONPs in vitro. Methods: A new approach of utilizing the leaf extract of Excoecaria agallocha was used to synthesize AgONPs. This was then characterized by ultraviolet-visible spectrophotometry, nanoparticle-tracking analysis, and ζ-potential analysis. Cytotoxicity and apoptotic potential were evaluated with an MTT assay and an annexin V-binding assay against the murine melanoma (B16F10), murine colon cancer (CT26), murine lung adenocarcinoma (3LL), and murine Ehrlich ascites carcinoma (EAC) cell lines. Cellular localization of AgONPs was evaluated on fluorescence microscopy. Results: UV peaks at 270 and 330 nm indicated the formation of nanoparticles (NPs) and the NP-tracking analyzer revealed them to have a size of 228 nm. AgONPs exerted initial cytotoxicity, specifically against all the experimental malignant cells by sparing the normal cell lines. Moreover, AgONPs exert apoptosis equally on all the malignant cells in vitro and ex vivo. This cytotoxicity possibly occurs via the nuclear translocation of AgONPs as analyzed in B16F10 cells. Conclusions: AgONPs utilizing natural sources would be a new medicinal approach against a broad spectrum of malignancy.

Keywords:
Silver oxide nanoparticles, Anticancer drugs, Green synthesis, Excoecaria agallocha L., Apoptosis, B16F10 melanoma
1.
Pérez J, Bax L, Escolano C; 6th Framework Programme (FP6) of the European Commission: Roadmap Report on Nanoparticles; NanoRoadMap (NRM) project, final report. Barcelona, Willems & van den Wildenberg, 2005.
2.
Kim JS, Kuk E, Yu KN, Kim JH, Park SJ, Lee HJ, Kim SH, Park YK, Park YH, Hwang CY, Kim YK, Lee YS, Jeong DH, Cho MH: Antimicrobial effects of silver nanoparticles. Nanomedicine 2007;3:95-101.
3.
Dar MA, Ingle A, Rai M: Enhanced antimicrobial activity of silver nanoparticles synthesized by Cryphonectria sp. evaluated singly and in combination with antibiotics. Nanomedicine 2013;9:105-110.
4.
Rai M, Yadav A, Gade A: Silver nanoparticles as a new generation of antimicrobials. Biotechnol Adv 2009;27:76-83.
5.
Sriram MI, Kanth SBM, Kalishwaralal K, Gurunathan S: Antitumor activity of silver nanoparticles in Dalton's lymphoma ascites tumor model. Int J Nanomed 2010;5:753-762.
6.
Hosseinpour-Mashkani SM, Ramezani M: Silver and silver oxide nanoparticles: synthesis and characterization by thermal decomposition. Mater Lett 2014;130:259-262.
7.
Rutberg FG, Dubina MV, Kolikov VA, Moiseenko FV, Ignat'eva EV, Volkov NM, Snetov VN, Stogov AY: Effect of silver oxide nanoparticles on tumor growth in vivo. Dokl Biochem Biophys 2008;421:191-193.
8.
Lara-González JH, Gomez-Flores R, Tamez-Guerra P, Monreal-Cuevas E, Tamez-Guerra R, Rodríguez-Padilla C: In vivo antitumor activity of metal silver and silver nanoparticles in the L5178Y-R murine lymphoma model. Br J Med Med Res 2013:3:1308-1316.
9.
Kalishwaralal K, Banumathi E, Pandian SRK, Deepak V, Muniyandi J, Eom SH, Gurunathan S: Silver nanoparticles inhibit VEGF induced cell proliferation and migration in bovine retinal endothelial cells. Colloid Surf B Biointerfaces 2009;73:51-57.
10.
Sheikpranbabu S, Kalishwaralal K, Venkataraman D, Eom SH, Park J, Gurunathan S: Silver nanoparticles inhibit VEGF-and IL-1beta-induced vascular permeability via Src dependent pathway in porcine retinal endothelial cells. J Nanobiotechnol 2009;7:8-19.
11.
Sheikpranbabu S, Kalishwaralal K, Lee KJ, Vaidyanathan R, Eom SH, Gurunathan S: The inhibition of advanced glycation end-products-induced retinal vascular permeability by silver nanoparticles. Biomaterials 2010;31:2260-2271.
12.
Kemp MM, Kumar A, Mousa S, Park TJ, Ajayan P, Kubotera N, Mousa SA, Linhardt RJ: Synthesis of gold and silver nanoparticles stabilized with glycosaminoglycans having distinctive biological activities. Biomacromolecules 2009;10:589-595.
13.
Sharma VK, Yngard RA, Yekaterina L: Silver nanoparticles: green synthesis and their antimicrobial activities. Adv Colloid Interface Sci 2009;145:83-96.
14.
Banerjee K, Ganguly A, Chakraborty P, Sarkar A, Singh S, Chatterjee M, Bhattacharya S, Choudhuri SK: ROS and RNS induced apoptosis through p53 and iNOS mediated pathway by a dibasic hydroxamic acid molecule in leukemia cells. Eur J Pharm Sci 2014;52:146-164.
15.
Fischer I, Petkau-Milroy K, Dorland YL, Schenning AP, Brunsveld L: Self-assembled fluorescent organic nanoparticles for live-cell imaging. Chemistry 2013;19:16646-16650.
16.
Rajanahalli P, Stucke CJ, Hong Y: The effects of silver nanoparticles on mouse embryonic stem cell self-renewal and proliferation. Toxicol Rep 2015;2:758-764.
17.
Ostrowski A, Nordmeyer D, Boreham A, Holzhausen C, Mundhenk L, Graf C, Meinke MC, Vogt A, Hadam S, Lademann J, Ruhl E, Alexiev U, Gruber AD: Overview about the localization of nanoparticles in tissue and cellular context by different imaging techniques. Beilstein J Nanotechnol 2015;6:263-280.
18.
Ingle A, Gade A, Pierrat S, Sonnichsen C, Rai M: Mycosynthesis of silver nanoparticles using the fungus Fusarium acuminatum and its activity against some human pathogenic bacteria. Curr Nanosci 2008;4:141-144.
19.
Jones SA, Bowler PG, Walker M, Parsons D: Controlling wound bioburden with a novel silver-containing Hydrofiber dressing. Wound Repair Regen 2004;12:288-294.
20.
Derjaguin BV, Landau LD: Theory of the stability of strongly charged lyophobic sols and of the adhesion of strongly charged particles in solutions of electrolytes. Acta Physicochim URSS 1941;14:633-662.
21.
Verwey EJW, Overbeek JTG: Theory of the Stability of Lyophobic Colloids. Amsterdam, Elsevier, 1948.
22.
Szmacinski H, Lakowicz JR, Catchmark JM, Eid K, Anderson JP, Middendorf L: Correlation between scattering properties of silver particle arrays and fluorescence enhancement. Appl Spectrosc 2008;62:733-738.
23.
Touahir L, Jenkins ATA, Boukherroub R, Gouget-Laemmel AC, Chazalviel JN, Peretti J, Ozanam F, Szunerits S: Surface plasmon-enhanced fluorescence spectroscopy on silver-based SPR substrates. J Phys Chem C 2010;114:22582-22589.
24.
Siegel R, Ma J, Zou Z, Jemal A: Cancer statistics, 2014. CA Cancer J Clin 2014;64:9-29.
25.
Liu H, Liu Y, Wang Z, He P: Facile synthesis of monodisperse, size-tunable SnS nanoparticles potentially for solar cell energy conversion. Nanotechnology 2010;21:105707.
26.
Espin JC, Garcia-Conesa MT, Thomas-Barberan FA: Nutraceuticals: facts and fiction. Phytochem 2007;68:2986-3008.
27.
Ksouri R, Falleh H, Megdiche W, Trabelsi N, Mhamdi B, Chaieb K, Bakrouf A, Magne C, Abdelly C: Antioxidant and antimicrobial activities of the edible medicinal halophyte Tamarix gallica L. and related polyphenolic constituents. Food Chem Toxicol 2009;47:2083-2091.
28.
Song JY, Kim BS: Rapid biological synthesis of silver nanoparticles using plant leaf extracts. Bioprocess Biosyst Eng 2009;32:79-84.
29.
Vijayaraghavan K, Nalini SK, Prakash NU, Madhankumar D: One step green synthesis of silver nano/microparticles using extracts of Trachyspermum ammi and Papaver somniferum. Colloids Surf B Biointerfaces 2012;94:114-117.
30.
Marković IS, Darmati ZA, Abramović BF: Chemical composition of leaf extracts of Stevia rebaudiana Bertoni grown experimentally in Vojvodina. J Serb Chem Soc 2008;73:283-297.
31.
Zheng CJ, Qin LP: Chemical components of Centella asiatica and their bioactives. J Chin Integr Med 2007;5:348-351.
32.
Hu R, Yong KT, Roy I, Ding H, He S, Prasad PN: Metallic nanostructures as localized plasmon resonance enhanced scattering probes for multiplex dark field targeted imaging of cancer cells. J Phys Chem C Nanomater Interfaces 2009;113:2676-2684.
33.
Noroozi M, Zakaria A, Moksin MM, Wahab Z, Abedini A: Green formation of spherical and dendritic silver nanostructures under microwave irradiation without reducing agent. Int J Mol Sci 2012;13:8086-8096.
34.
Gurunathan S, Kalishwaralal K, Vaidyanathan R, Venkataraman D, Pandian SR, Muniyandi J, Hariharan N, Eom SH: Biosynthesis, purification and characterization of silver nanoparticles using Escherichia coli. Colloids Surf B Biointerfaces 2009;74:328-335.
35.
Tan K, Cheang P, Ho IA, Lam PY, Hui KM: Nanosized bioceramic particles could function as efficient gene delivery vehicles with target specificity for the spleen. Gene Ther 2007;14:828-835.
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