Login Register Cart 0
Generic placeholder image

Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Letter Article

Oxidative Stress Induced Cell Cycle Arrest: Potential Role of PRX-2 and GSTP-1 as Therapeutic Targets in Hepatocellular Carcinoma

Author(s): Abeer Mohsin, Kanwal Haneef, Amber Ilyas, Shamshad Zarina and Zehra Hashim*

Volume 28, Issue 12, 2021

Published on: 26 November, 2021

Page: [1323 - 1329] Pages: 7

DOI: 10.2174/0929866528666211105105953

Price: $65

Abstract

Background: The increasing incidence and mortality rate of HCC is a major concern, especially for developing countries of the world. Hence, extensive research is being carried out in order to explore new approaches for developing successful therapeutic strategies for HCC. The controversial role of oxidative stress in the prognosis and treatment of various diseases such as cancer has become an area of great interest and intrigue for many scientists throughout the world.

Objective: We aim to investigate the role of induced oxidative stress on the suppression of HCC Huh-7 cancerous cells as a therapeutic approach.

Methods: Induction of oxidative stress via H2O2 treatment produced cell cytotoxicity in a dose dependent manner and also led to the overexpression of GSTP-1 and PRX-2. The expression of GSTP- 1 and PRX-2 was compared in HCC Huh-7 treated, untreated cells and normal hepatocytes using immunocytochemistry. Furthermore, the effects of oxidative stress on cell cycle arrest were also studied through flow cytometry.

Results: Our study demonstrated the inhibition of cancer cell proliferation as a result of H2O2 induction by arresting the cell cycle at the G2 phase.

Conclusion: The induction of oxidative stress could be a potential therapeutic approach for treating HCC in the future. GSTP-1 and PRX-2 can serve as substantial therapeutic targets for the treatment of HCC.

Keywords: Hepatocellular carcinoma, oxidative stress, H2O2, reactive oxygen species, cancer therapy, glutathione S-transferase, peroxiredoxin-2, cell cycle

Next »
Graphical Abstract

[1]
Hejmadi, M. Introduction to cancer biology; Bookboon, 2014.
[2]
Jemal, A.; Bray, F.; Center, M.M.; Ferlay, J.; Ward, E.; Forman, D. Global cancer statistics. CA Cancer J. Clin., 2011, 61(2), 69-90.
[http://dx.doi.org/10.3322/caac.20107] [PMID: 21296855]
[3]
Bray, F.; Jemal, A.; Grey, N.; Ferlay, J.; Forman, D. Global cancer transitions according to the Human Development Index (2008-2030): a population-based study. Lancet Oncol., 2012, 13(8), 790-801.
[http://dx.doi.org/10.1016/S1470-2045(12)70211-5] [PMID: 22658655]
[4]
Starley, B.Q.; Calcagno, C.J.; Harrison, S.A. Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology, 2010, 51(5), 1820-1832.
[http://dx.doi.org/10.1002/hep.23594] [PMID: 20432259]
[5]
Park, S.H.; Heo, N.Y.; Park, J.H.; Kim, T.O.; Yang, S.Y.; Kim, H.K.; Moon, Y.S.; Kim, C.H.; Suk, K.T.; Kim, D.J.; Lee, H.Y. Hepatocellular carcinoma screening in a hepatitis B virus-infected Korean population. Dig. Dis. Sci., 2012, 57(12), 3258-3264.
[http://dx.doi.org/10.1007/s10620-012-2281-6] [PMID: 22729598]
[6]
Yang, J.D.; Roberts, L.R. Hepatocellular carcinoma: A global view. Nat. Rev. Gastroenterol. Hepatol., 2010, 7(8), 448-458.
[http://dx.doi.org/10.1038/nrgastro.2010.100] [PMID: 20628345]
[7]
Butt, A.S. Epidemiology of viral hepatitis and liver diseases in Pakistan. Euroasian J. Hepatogastroenterol., 2015, 5(1), 43-48.
[http://dx.doi.org/10.5005/jp-journals-10018-1129] [PMID: 29201686]
[8]
Abbas, Z. Hepatocellular carcinoma in Pakistan. J. Coll. Physicians Surg. Pak., 2013, 23(10), 769-770.
[PMID: 24169381]
[9]
Hafeez Bhatti, A.B.; Dar, F.S.; Waheed, A.; Shafique, K.; Sultan, F.; Shah, N.H. Hepatocellular carcinoma in Pakistan: national trends and global perspective. Gastroenterol. Res. Pract., 2016, 2016, 5942306.
[http://dx.doi.org/10.1155/2016/5942306] [PMID: 26955390]
[10]
Tsuchiya, N.; Sawada, Y.; Endo, I.; Saito, K.; Uemura, Y.; Nakatsura, T. Biomarkers for the early diagnosis of hepatocellular carcinoma. World J. Gastroenterol., 2015, 21(37), 10573-10583.
[http://dx.doi.org/10.3748/wjg.v21.i37.10573] [PMID: 26457017]
[11]
Herceg, Z.; Paliwal, A. Epigenetic mechanisms in hepatocellular carcinoma: how environmental factors influence the epigenome. Mutat. Res., 2011, 727(3), 55-61.
[http://dx.doi.org/10.1016/j.mrrev.2011.04.001] [PMID: 21514401]
[12]
Parkash, O.; Hamid, S. Next big threat for Pakistan Hepatocellular Carcinoma (HCC). J. Pak. Med. Assoc., 2016, 66(6), 735-739.
[PMID: 27339578]
[13]
Pisoschi, A.M.; Pop, A. The role of antioxidants in the chemistry of oxidative stress: A review. Eur. J. Med. Chem., 2015, 97, 55-74.
[http://dx.doi.org/10.1016/j.ejmech.2015.04.040] [PMID: 25942353]
[14]
Valko, M.; Rhodes, C.J.B.; Moncol, J.; Izakovic, M.; Mazur, M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem. Biol. Interact., 2006, 160(1), 1-40.
[http://dx.doi.org/10.1016/j.cbi.2005.12.009] [PMID: 16430879]
[15]
Reuter, S.; Gupta, S.C.; Chaturvedi, M.M.; Aggarwal, B.B. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic. Biol. Med., 2010, 49(11), 1603-1616.
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.09.006] [PMID: 20840865]
[16]
Liu, J.; Wang, Z. Increased oxidative stress as a selective anticancer therapy. Oxid. Med. Cell. Longev., 2015, 2015(13), 294303.
[http://dx.doi.org/10.1155/2015/294303] [PMID: 26273420]
[17]
Sosa, V.; Moliné, T.; Somoza, R.; Paciucci, R.; Kondoh, H.; LLeonart, M.E. Oxidative stress and cancer: an overview. Ageing Res. Rev., 2013, 12(1), 376-390.
[http://dx.doi.org/10.1016/j.arr.2012.10.004] [PMID: 23123177]
[18]
Hashim, Z.; Ilyas, A.; Zarina, S. Therapeutic effect of hydrogen peroxide via altered expression of glutathione S-transferase and peroxiredoxin-2 in hepatocellular carcinoma. Hepatobiliary Pancreat. Dis. Int., 2020, 19(3), 258-265.
[http://dx.doi.org/10.1016/j.hbpd.2020.03.006] [PMID: 32284258]
[19]
Halliwell, B. Oxidative stress and cancer: have we moved forward? Biochem. J., 2007, 401(1), 1-11.
[http://dx.doi.org/10.1042/BJ20061131] [PMID: 17150040]
[20]
Hayes, J.D.; Dinkova-Kostova, A.T.; Tew, K.D. Oxidative stress in cancer. Cancer Cell,, 2020, 38(2), 167-197.
[http://dx.doi.org/10.1016/j.ccell.2020.06.001] [PMCID: PMC7439808]
[21]
Madunić, I.V.; Madunić, J.; Antunović, M.; Paradžik, M.; Garaj-Vrhovac, V.; Breljak, D.; Marijanović, I.; Gajski, G. Apigenin, a dietary flavonoid, induces apoptosis, DNA damage, and oxidative stress in human breast cancer MCF-7 and MDA MB-231 cells. Naunyn Schmiedebergs Arch. Pharmacol,, 2018, 391(5), 537-550.
[http://dx.doi.org/10.1007/s00210-018-1486-4] [PMID: 29541820]
[22]
Barrera, G., Oxidative stress and lipid peroxidation products in cancer progression and therapy. ISRN Oncol., 2012, 2012, 1-22.
[http://dx.doi.org/10.5402/2012/137289] [PMID: 23119185]
[23]
Schumacker, P.T., Reactive oxygen species in cancer: a dance with the devil. Cancer Cell, 2015, 27(2), 156-157.
[http://dx.doi.org/10.1016/j.ccell.2015.01.007] [PMID: 25670075]
[24]
Vilema-Enríquez, G., Arroyo, A., Grijalva, M., Amador-Zafra, R.I. : Camacho, J., Molecular and cellular effects of hydrogen peroxide on human lung cancer cells: potential therapeutic implications. Oxid. Med. Cell. Longev.,, 2016, 2016, 1-13.
[http://dx.doi.org/10.1155/2016/1908164] [PMID: 27375834]
[25]
Hadzic, T.; Aykin-Burns, N.; Zhu, Y.; Coleman, M.C.; Leick, K.; Jacobson, G.M.; Spitz, D.R. Paclitaxel combined with inhibitors of glucose and hydroperoxide metabolism enhances breast cancer cell killing via H2O2-mediated oxidative stress. Free Radic. Biol. Med., 2010, 48(8), 1024-1033.
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.01.018] [PMID: 20083194]
[26]
Vrhovac Madunić, I.; Madunić, J.; Antunović, M.; Paradžik, M.; Garaj-Vrhovac, V.; Breljak, D.; Marijanović, I.; Gajski, G. Apigenin, a dietary flavonoid, induces apoptosis, DNA damage, and oxidative stress in human breast cancer MCF-7 and MDA MB-231 cells. Naunyn Schmiedebergs Arch. Pharmacol., 2018, 391(5), 537-550.
[http://dx.doi.org/10.1007/s00210-018-1486-4] [PMID: 29541820]
[27]
Noh, J.; Kwon, B.; Han, E.; Park, M.; Yang, W.; Cho, W.; Yoo, W.; Khang, G.; Lee, D. Amplification of oxidative stress by a dual stimuli-responsive hybrid drug enhances cancer cell death. Nat. Commun., 2015, 6(1), 6907.
[http://dx.doi.org/10.1038/ncomms7907] [PMID: 25892552]
[28]
Uetaki, M.; Tabata, S.; Nakasuka, F.; Soga, T.; Tomita, M. Metabolomic alterations in human cancer cells by vitamin C-induced oxidative stress. Sci. Rep., 2015, 5(1), 13896.
[http://dx.doi.org/10.1038/srep13896] [PMID: 26350063]
[29]
Rehman, K.; Akash, M.S.H. Mechanism of generation of oxidative stress and pathophysiology of type 2 diabetes mellitus: how are they interlinked? J. Cell. Biochem., 2017, 118(11), 3577-3585.
[http://dx.doi.org/10.1002/jcb.26097] [PMID: 28460155]
[30]
Pizzino, G.; Irrera, N.; Cucinotta, M.; Pallio, G.; Mannino, F.; Arcoraci, V.; Squadrito, F.; Altavilla, D.; Bitto, A. Oxidative stress: harms and benefits for human health. Oxid. Med. Cell. Longev., 2017, 2017, 8416763.
[http://dx.doi.org/10.1155/2017/8416763] [PMID: 28819546]
[31]
Schafer, K.A. The cell cycle: a review. Vet. Pathol., 1998, 35(6), 461-478.
[http://dx.doi.org/10.1177/030098589803500601] [PMID: 9823588]
[32]
Zhang, X.; Chen, M.; Zou, P.; Kanchana, K.; Weng, Q.; Chen, W.; Zhong, P.; Ji, J.; Zhou, H.; He, L.; Liang, G. Curcumin analog WZ35 induced cell death via ROS-dependent ER stress and G2/M cell cycle arrest in human prostate cancer cells. BMC Cancer, 2015, 15(1), 866.
[http://dx.doi.org/10.1186/s12885-015-1851-3] [PMID: 26546056]
[33]
Li, W.; Xie, L.; Chen, Z.; Zhu, Y.; Sun, Y.; Miao, Y.; Xu, Z.; Han, X. Cantharidin, a potent and selective PP2A inhibitor, induces an oxidative stress-independent growth inhibition of pancreatic cancer cells through G2/M cell-cycle arrest and apoptosis. Cancer Sci., 2010, 101(5), 1226-1233.
[http://dx.doi.org/10.1111/j.1349-7006.2010.01523.x] [PMID: 20331621]
[34]
Chang, Y.T.; Wu, C.Y.; Tang, J.Y.; Huang, C.Y.; Liaw, C.C.; Wu, S.H.; Sheu, J.H.; Chang, H.W. Sinularin induces oxidative stress-mediated G2/M arrest and apoptosis in oral cancer cells. Environ. Toxicol., 2017, 32(9), 2124-2132.
[http://dx.doi.org/10.1002/tox.22425] [PMID: 28548367]
[35]
Yang, J.; Huo, T.; Zhang, X.; Ma, J.; Wang, Y.; Dong, F.; Deng, J. Oxidative stress and cell cycle arrest induced by short-term exposure to dustfall PM2.5 in A549 cells. Environ. Sci. Pollut. Res. Int., 2018, 25(23), 22408-22419.
[http://dx.doi.org/10.1007/s11356-017-0430-3] [PMID: 29098582]
[36]
Hasanzadeh, D.; Mahdavi, M.; Dehghan, G.; Charoudeh, H.N. Farnesiferol C induces cell cycle arrest and apoptosis mediated by oxidative stress in MCF-7 cell line. Toxicol. Rep., 2017, 4, 420-426.
[http://dx.doi.org/10.1016/j.toxrep.2017.07.010] [PMID: 28959668]
[37]
Ramalingam, V.; Revathidevi, S.; Shanmuganayagam, T.; Muthulakshmi, L.; Rajaram, R. Biogenic gold nanoparticles induce cell cycle arrest through oxidative stress and sensitize mitochondrial membranes in A549 lung cancer cells. RSC Advances, 2016, 6(25), 20598-20608.
[http://dx.doi.org/10.1039/C5RA26781A]
[38]
Li, T.; Zhao, X.P.; Wang, L.Y.; Gao, S.; Zhao, J.; Fan, Y.C.; Wang, K. Glutathione S-transferase P1 correlated with oxidative stress in hepatocellular carcinoma. Int. J. Med. Sci., 2013, 10(6), 683-690.
[http://dx.doi.org/10.7150/ijms.5947] [PMID: 23569432]
[39]
Liu, X.; Tan, N.; Liao, H.; Pan, G.; Xu, Q.; Zhu, R.; Zou, L.; He, S.; Zhu, H. High GSTP1 inhibits cell proliferation by reducing Akt phosphorylation and is associated with a better prognosis in hepatocellular carcinoma. Oncotarget, 2017, 9(10), 8957-8971.
[http://dx.doi.org/10.18632/oncotarget.23420] [PMID: 29507666]
[40]
Gao, L.; Fang, Y.Q.; Zhang, T.Y.; Ge, B.; Xu, B.; Huang, J.F.; Zhang, Z.F.; Tan, N. GSTP1 arrests bladder cancer T24 cells in G0/G1 phase and up-regulates p21 expression. Int. J. Clin. Exp. Med., 2014, 7(9), 2984-2991.
[PMID: 25356172]
[41]
Ripani, P.; Delp, J.; Bode, K.; Delgado, M.E.; Dietrich, L.; Betzler, V.M.; Yan, N.; von Scheven, G.; Mayer, T.U.; Leist, M.; Brunner, T. Thiazolides promote G1 cell cycle arrest in colorectal cancer cells by targeting the mitochondrial respiratory chain. Oncogene, 2020, 39(11), 2345-2357.
[http://dx.doi.org/10.1038/s41388-019-1142-6] [PMID: 31844249]
[42]
Khan, N.; Mukhtar, H. Modulation of signaling pathways in prostate cancer by green tea polyphenols. Biochem. Pharmacol., 2013, 85(5), 667-672.
[http://dx.doi.org/10.1016/j.bcp.2012.09.027] [PMID: 23041649]
[43]
Martignano, F.; Gurioli, G.; Salvi, S.; Calistri, D.; Costantini, M.; Gunelli, R.; De Giorgi, U.; Foca, F.; Casadio, V. GSTP1 methylation and protein expression in prostate cancer: diagnostic implications. Dis. Markers, 2016, 2016, 4358292.
[http://dx.doi.org/10.1155/2016/4358292] [PMID: 27594734]
[44]
Kim, Y.; Jang, H.H. Role of Cytosolic 2-Cys Prx1 and Prx2 in Redox Signaling. Antioxidants, 2019, 8(6), 169-174.
[http://dx.doi.org/10.3390/antiox8060169] [PMID: 31185618]
[45]
Kim, Y.; Jang, H.H. The role of peroxiredoxin family in cancer signaling. J. Cancer Prev., 2019, 24(2), 65-71.
[http://dx.doi.org/10.15430/JCP.2019.24.2.65] [PMID: 31360686]
[46]
Nicolussi, A.; D’Inzeo, S.; Capalbo, C.; Giannini, G.; Coppa, A. The role of peroxiredoxins in cancer. Mol. Clin. Oncol., 2017, 6(2), 139-153.
[http://dx.doi.org/10.3892/mco.2017.1129] [PMID: 28357082]
[47]
Ilyas, A.; Hashim, Z.; Naeem, N.; Haneef, K.; Zarina, S. The effect of alendronate on proteome of hepatocellular carcinoma cell lines. Int. J. Proteomics, 2014, 2014, 532953.
[http://dx.doi.org/10.1155/2014/532953] [PMID: 24653834]

Rights & Permissions Print Cite
Article Metrics
30
1
© 2024 Bentham Science Publishers | Privacy Policy