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Current Nutraceuticals


ISSN (Print): 2665-9786
ISSN (Online): 2665-9794

Research Article

Hydrogen Peroxide and Quercetin Induced Changes on Cell Viability, Apoptosis and Oxidative Stress in HepG2 Cells

Author(s): Ayşe Mine Yılmaz, Gökhan Biçim, Kübra Toprak, Betül Karademir Yılmaz, Irina Milisav and Ahmet Suha Yalçın*

Volume 2, Issue 1, 2021

Published on: 07 August, 2020

Page: [47 - 55] Pages: 9

DOI: 10.2174/2665978601999200807160528


Background: Different cellular responses influence the progress of cancer. In this study, the effects of hydrogen peroxide and quercetin induced changes on cell viability, apoptosis, and oxidative stress in human hepatocellular carcinoma (HepG2) cells were investigated.

Methods: The effects of hydrogen peroxide and quercetin on cell viability, cell cycle phases, and oxidative stress related cellular changes were investigated. Cell viability was assessed by WST-1 assay. Apoptosis rate, cell cycle phase changes, and oxidative stress were measured by flow cytometry. Protein expressions of p21, p27, p53, NF-Kβ-p50, and proteasome activity were determined by Western blot and fluorometry, respectively.

Results: Hydrogen peroxide and quercetin treatment resulted in decreased cell viability and increased apoptosis in HepG2 cells. Proteasome activity was increased by hydrogen peroxide but decreased by quercetin treatment.

Conclusion: Both agents resulted in decreased p53 protein expression and increased cell death by different mechanisms regarding proteostasis and cell cycle phases.

Keywords: HepG2 cells, oxidative stress, hydrogen peroxide, quercetin, apoptosis, cell cycle.

Graphical Abstract
Muniafu, M.; Kahindi, J.H.P. Phytochemicals, natural products at a crossroad: Current and future directions. Planta Med., 2013, 79, 874-875.
Pavlović, I.; Khateb, S.; Milisav, I.; Mahajna, J. Nutraceuticals for promoting longevity. Curr. Nutr., 2020, 1, 1-18.
Ramalingum, N.; Mahomoodally, M.F. The therapeutic potential of medicinal foods. Adv. Pharmacol. Sci., 2014, 2014354264
Wang, T.; Wang, Q.; Li, P.; Yang, H. Temperature-responsive ionic liquids to set up a method for the simultaneous extraction and in situ preconcentration of hydrophilic and lipophilic compounds from medicinal plant matrices. Green Chem., 2019, 21, 4133-4142.
Griffin, S.; Tittikpina, N.K.; Al-marby, A.; Alkhayer, R.; Denezhkin, P.; Witek, K.; Gbogbo, K.A.; Batawila, K.; Duval, R.E.; Nasim, M.J.; Awadh-Ali, N.A.; Kirsch, G.; Chaimbault, P.; Schäfer, K-H.; Keck, C.M.; Handzlik, J.; Jacob, C. Turning waste into value: nanosized natural plant materials of solanum incanum L. and pterocarpus erinaceus poir with promising antimicrobial activities. Pharmaceutics, 2016, 8, 11.
Griffin, S.; Masood, M.I.; Nasim, M.J.; Sarfraz, M.; Ebokaiwe, A.P.; Schafer, K.H.; Keck, C.M.; Jacob, C. Natural nanoparticles: A particular matter inspired by nature. Antioxidants, 2017, 7, 1-21.
Griffin, S.; Alkhayer, R.; Mirzoyan, S.; Turabyan, A.; Zucca, P.; Sarfraz, M.; Nasim, M.; Trchounian, A.; Rescigno, A.; Keck, C.; Jacob, C. Nanosizing cynomorium: Thumbs up for potential antifungal applications. Inventions, 2017, 2, 24.
Griffin, S.; Sarfraz, M.; Farida, V.; Nasim, M.J.; Ebokaiwe, A.P.; Keck, C.M.; Jacob, C. No time to waste organic waste: Nanosizing converts remains of food processing into refined materials. J. Environ. Manage., 2018, 210, 114-121.
Sarfraz, M.; Griffin, S.; Gabour Sad, T.; Alhasan, R.; Nasim, M.J.; Irfan Masood, M.; Schafer, K.H.; Ejike, C.; Keck, C.M.; Jacob, C.; Ebokaiwe, A.P. Milling the mistletoe: Nanotechnological conversion of african mistletoe (Loranthus micranthus) intoantimicrobial materials. Antioxidants, 2018, 7, 1-10.
Dizaj, S.M.; Vazifehasl, Z.; Salatin, S.; Adibkia, K.; Javadzadeh, Y. Nanosizing of drugs: Effect on dissolution rate. Res. Pharm. Sci., 2015, 10, 95-108.
Al-Kassas, R.; Bansal, M.; Shaw, J. Nanosizing techniques for improving bioavailability of drugs. J. Control. Release, 2017, 260, 202-212.
Lai, F.; Schlich, M.; Pireddu, R.; Corrias, F.; Fadda, A.M.; Sinico, C. Production of nanosuspensions as a tool to improve drug bioavailability: Focus on topical delivery. Curr. Pharm. Des., 2015, 21, 6089-6103.
Schrader, I.; Warneke, J.; Neumann, S.; Grotheer, S.; Swane, A.A.; Kirkensgaard, J.J.K.; Arenz, M.; Kunz, S. Surface chemistry of “unprotected” nanoparticles: A spectroscopic investigation on colloidal particles. J. Phys. Chem. C, 2015, 119, 17655-17661.
Conde, J.; Dias, J.T.; Grazu, V.; Moros, M.; Baptista, P.V.; de la Fuente, J.M. Revisiting 30 years of biofunctionalization and surface chemistry of inorganic nanoparticles for nanomedicine. Front Chem., 2014, 2, 1-27.
Biener, J.; Wittstock, A.; Baumann, T.F.; Weissmuller, J.; Baumer, M.; Hamza, A.V. Surface chemistry in nanoscale materials. Materials (Basel), 2009, 2, 2404-2428.
Gatoo, M.A.; Naseem, S.; Arfat, M.Y.; Dar, A.M.; Qasim, K.; Zubair, S. Physicochemical properties of nanomaterials: Implication in associated toxic manifestations. BioMed Res. Int., 2014.
Turci, F.; Tomatis, M.; Lesci, I.G.; Roveri, N.; Fubini, B. The iron-related molecular toxicity mechanism of synthetic asbestos nanofibres: A model study for high-aspect-ratio nanoparticles. Chem Eur. J,, 2011, 17, 350-358.
Ahmad, A.; Husain, A.; Mujeeb, M.; Khan, S.A.; Najmi, A.K.; Siddique, N.A.; Damanhouri, Z.A.; Anwar, F. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac. J. Trop. Biomed., 2013, 3, 337-352.
Kooti, W.; Hasanzadeh-Noohi, Z.; Sharafi-Ahvazi, N.; Asadi-Samani, M.; Ashtary-Larky, D. Phytochemistry, pharmacology, and therapeutic uses of black seed (Nigella sativa). Chin. J. Nat. Med., 2016, 14, 732-745.
Mohammed, N.K.; Muhialdin, B.J.; Hussin, A.S.M. Characterization of nanoemulsion of Nigella sativa oil and its application in ice cream. Food Sci. Nutr., 2020, 8, 2608-2618.
Muthumanickkam, A.; Subramanian, S.; Sathiyaraj, M.; Preethi, P.; Ashwini, M. Development of herb based (Nigella sativa) eri silk nanofibrous mat for biomedical applications. Mater. Today Proc., 2020, 22, 585-588.
Forouzanfar, F.; Bazzaz, B.S.F.; Hosseinzadeh, H. Black cumin (Nigella sativa) and its constituent (thymoquinone): A review on antimicrobial effects. Iran. J. Basic Med. Sci., 2014, 17, 929-938.
Mukhtar, H.; Qureshi, A.S.; Anwar, F.; Mumtaz, M.W.; Marcu, M. Nigella sativa L. seed and seed oil: Potential sources of high-value components for development of functional foods and nutraceuticals/pharmaceuticals. J. Essent. Oil Res., 2019, 31, 171-183.
Islam, M.T.; Khan, M.; Mishra, S.K. An updated literature-based review: Phytochemistry, pharmacology and therapeutic promises of Nigella sativa L. Orient. Pharm. Exp. Med., 2019, 19, 115-129.
Estevam, E.C.; Griffin, S.; Nasim, M.J.; Denezhkin, P.; Schneider, R.; Lilischkis, R.; Dominguez-Alvarez, E.; Witek, K.; Latacz, G.; Keck, C. Natural selenium particles from Staphylococcus carnosus: Hazards or particles with particular promise? J. Hazard. Mater., 2017, 324, 22-30.
Manikova, D.; Letavayova, L.M.; Vlasakova, D.; Kosik, P.; Estevam, E.C.; Nasim, M.J.; Gruhlke, M.; Slusarenko, A.; Burkholz, T.; Jacob, C.; Chovanec, M. Intracellular diagnostics: Hunting for the mode of action of redox-modulating selenium compounds in selected model systems. Molecules, 2014, 19, 12258-12279.
Castellucci Estevam, E.; Witek, K.; Faulstich, L.; Nasim, M.J.; Latacz, G.; Dominguez-Alvarez, E.; Kiec-Kononowicz, K.; Demasi, M.; Handzlik, J.; Jacob, C. Aspects of a distinct cytotoxicity of selenium salts and organic selenides in living cells with possible implications for drug design. Molecules, 2015, 20, 13894-13912.
Shimamura, T.S.Y.; Yamazaki, T.; Tada, A.; Kashiwagi, T.; Ishikawa, H.; Matsui, T.; Sugimoto, N.; Akiyama, H.; Ukeda, H. Applicability of the DPPH assay for evaluating the antioxidant capacity of food additives - inter-laboratory evaluation study. Anal. Sci., 2014, 30, 717-721.
Loganayaki, N.; Siddhuraju, P.; Manian, S. Antioxidant activity and free radical scavenging capacity of phenolic extracts from Helicteres isora L. and Ceiba pentandra L. J. Food Sci. Tech. Mys., 2013, 50, 687-695.
Moteriya, P.; Padalia, H.; Chanda, S. Characterization, synergistic antibacterial and free radical scavenging efficacy of silver nanoparticles synthesized using Cassia roxburghii leaf extract. J. Genet. Eng. Biotechnol., 2017, 15, 505-513.
Benzie, I.F.; Strain, J.J. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: The FRAP assay. Anal. Biochem., 1996, 239, 70-76.
Arokiyaraj, S.; Bharanidharan, R.; Agastian, P.; Shin, H. Chemical composition, antioxidant activity and antibacterial mechanism of action from Marsilea minuta leaf hexane: Methanol extract. Chem. Cent. J., 2018, 12, 1-11.
Zarrouk, A.; Martine, L.; Grégoire, S.; Nury, T.; Meddeb, W.; Camus, E.; Badreddine, A.; Durand, P.; Namsi, A.; Yammine, A.; Nasser, B.; Mejri, M.; Bretillon, L.; Mackrill, J.J.; Cherkaoui-Malki, M.; Hammami, M.; Lizard, G. Profile of fatty acids, tocopherols, phytosterols and polyphenols in Mediterranean oils (argan oils, olive oils, milk thistle seed oils and nigella seed oil) and evaluation of their antioxidant and cytoprotective activities. Curr. Pharm. Des., 2019, 25, 1791-1805.
Fathima, J.B.; Pugazhendhi, A.; Venis, R. Synthesis and characterization of ZrO2 nanoparticles-antimicrobial activity and their prospective role in dental care. Microb. Pathog., 2017, 110, 245-251.
Pandiyan, N.; Murugesan, B.; Sonamuthu, J.; Samayanan, S.; Mahalingam, S. Facile biological synthetic strategy to morphologically aligned CeO2/ZrO2 core nanoparticles using Justicia adhatoda extract and ionic liquid: Enhancement of its bio-medical properties. J. Photochem. Photobiol. B, 2018, 178, 481-488.
Schlesinger, M.E.; King, M.J.; Sole, K.C.; Davenport, W.G. Chapter 3 - Production of high copper concentrates – Introduction and comminution. In: Extractive Metallurgy of Copper (Fifth Edition); Schlesinger, M.E.; King M.J.; Sole, K.C.; Davenport, W.G.; eds.; Elsevier: Oxford, 2011, pp. 31-49..
Huber, D.L. Synthesis, properties, and applications of iron nanoparticles. Small, 2005, 1, 482-501.
Robertson, J.D.; Rizzello, L.; Avila-Olias, M.; Gaitzsch, J.; Contini, C.; Magon, M.S.; Renshaw, S.A.; Battaglia, G. Purification of nanoparticles by size and shape. Sci. Rep., 2016, 6, 1-9.
Liu, X.F.; Kang, J.M.; Liu, B.; Yang, J.H. Separation of gold nanowires and nanoparticles through a facile process of centrifugation. Separ. Purif. Tech., 2018, 192, 1-4.
Xiong, B.; Cheng, J.; Qiao, Y.X.; Zhou, R.; He, Y.; Yeung, E.S. Separation of nanorods by density gradient centrifugation. J. Chromatogr. A, 2011, 1218, 3823-3829.

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