Direct Interaction between N-Acetylcysteine and Cytotoxic Electrophile-An Overlooked In Vitro Mechanism of Protection

. 2022 Jul 29 ; 11 (8) : . [epub] 20220729

Status PubMed-not-MEDLINE Jazyk angličtina Země Švýcarsko Médium electronic

Typ dokumentu časopisecké články, přehledy

Perzistentní odkaz   https://www.medvik.cz/link/pmid36009205

Grantová podpora
IGA_LF_2022_034 Palacký University, Olomouc

In laboratory experiments, many electrophilic cytotoxic agents induce cell death accompanied by reactive oxygen species (ROS) production and/or by glutathione (GSH) depletion. Not surprisingly, millimolar concentrations of N-acetylcysteine (NAC), which is used as a universal ROS scavenger and precursor of GSH biosynthesis, inhibit ROS production, restore GSH levels, and prevent cell death. The protective effect of NAC is generally used as corroborative evidence that cell death induced by a studied cytotoxic agent is mediated by an oxidative stress-related mechanism. However, any simple interpretation of the results of the protective effects of NAC may be misleading because it is unable to interact with superoxide (O2•-), the most important biologically relevant ROS, and is a very weak scavenger of H2O2. In addition, NAC is used in concentrations that are unnecessarily high to stimulate GSH synthesis. Unfortunately, the possibility that NAC as a nucleophile can directly interact with cytotoxic electrophiles to form non-cytotoxic NAC-electrophile adduct is rarely considered, although it is a well-known protective mechanism that is much more common than expected. Overall, apropos the possible mechanism of the cytoprotective effect of NAC in vitro, it is appropriate to investigate whether there is a direct interaction between NAC and the cytotoxic electrophile to form a non-cytotoxic NAC-electrophilic adduct(s).

Zobrazit více v PubMed

Flanagan R.J., Meredith T. Use of N-acetylcysteine in clinical toxicology. Am. J. Med. 1991;91:131S–139S. doi: 10.1016/0002-9343(91)90296-A. PubMed DOI

Kelly G.S. Clinical applications of N-acetylcysteine. Altern. Med. Rev. J. Clin. Ther. 1998;3:114–127. PubMed

Millea P.J. N-acetylcysteine: Multiple clinical applications. Am. Fam. Physician. 2009;80:265–269. PubMed

Samuni Y., Goldstein S., Dean O.M., Berk M. The chemistry and biological activities of N-acetylcysteine. Biochim. Biophys. Acta. 2013;1830:4117–4129. doi: 10.1016/j.bbagen.2013.04.016. PubMed DOI

Rushworth G.F., Megson I.L. Existing and potential therapeutic uses for N-acetylcysteine: The need for conversion to intracellular glutathione for antioxidant benefits. Pharmacol. Ther. 2014;141:150–159. doi: 10.1016/j.pharmthera.2013.09.006. PubMed DOI

Tardiolo G., Bramanti P., Mazzon E. Overview on the Effects of N-Acetylcysteine in Neurodegenerative Diseases. Molecules. 2018;23:3305. doi: 10.3390/molecules23123305. PubMed DOI PMC

Šalamon Š., Kramar B., Marolt T.P., Poljšak B., Milisav I. Medical and Dietary Uses of N-Acetylcysteine. Antioxidants. 2019;8:111. doi: 10.3390/antiox8050111. PubMed DOI PMC

Schwalfenberg G.K. N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks) J. Nutr. Metab. 2021;2021:9949453. doi: 10.1155/2021/9949453. PubMed DOI PMC

De Flora S., Cesarone C.F., Balansky R.M., Albini A., D’Agostini F., Bennicelli C., Bagnasco M., Camoirano A., Scatolini L., Rovida A., et al. Chemopreventive properties and mechanisms of N-Acetylcysteine. The experimental background. J. Cell Biochem. Suppl. 1995;22:33–41. doi: 10.1002/jcb.240590806. PubMed DOI

Zhitkovich A. N-Acetylcysteine: Antioxidant, Aldehyde Scavenger, and More. Chem. Res. Toxicol. 2019;32:1318–1319. doi: 10.1021/acs.chemrestox.9b00152. PubMed DOI PMC

Ezeriņa D., Takano Y., Hanaoka K., Urano Y., Dick T.P. N-Acetyl Cysteine Functions as a Fast-Acting Antioxidant by Triggering Intracellular H2S and Sulfane Sulfur Production. Cell Chem. Biol. 2018;25:447–459.e4. doi: 10.1016/j.chembiol.2018.01.011. PubMed DOI PMC

Zafarullah M., Li W.Q., Sylvester J., Ahmad M. Molecular mechanisms of N-acetylcysteine actions. Cell. Mol. Life Sci. 2003;60:6–20. doi: 10.1007/s000180300001. PubMed DOI PMC

Luczak M.W., Zhitkovich A. Role of direct reactivity with metals in chemoprotection by N-acetylcysteine against chromium(VI), cadmium(II), and cobalt(II) Free Radic. Biol. Med. 2013;65:262–269. doi: 10.1016/j.freeradbiomed.2013.06.028. PubMed DOI PMC

Phaniendra A., Jestadi D.B., Periyasamy L. Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases. Indian J. Clin. Biochem. 2015;30:11–26. doi: 10.1007/s12291-014-0446-0. PubMed DOI PMC

Thannickal V.J., Fanburg B.L. Reactive oxygen species in cell signaling. Am. J. Physiol. Cell. Mol. Physiol. 2000;279:L1005–L1028. doi: 10.1152/ajplung.2000.279.6.L1005. PubMed DOI

Valko M., Leibfritz D., Moncol J., Cronin M.T.D., Mazur M., Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol. 2007;39:44–84. doi: 10.1016/j.biocel.2006.07.001. PubMed DOI

Sundaresan M., Yu Z.-X., Ferrans V.J., Sulciner D.J., Gutkind J.S., Irani K., Goldschmidt-Clermont P.J., Finkel T. Regulation of reactive-oxygen-species generation in fibroblasts by Rac 1. Pt 2Biochem. J. 1996;318:379–382. doi: 10.1042/bj3180379. PubMed DOI PMC

Palmer H.J., Paulson K.E. Reactive Oxygen Species and Antioxidants in Signal Transduction and Gene Expression. Nutr. Rev. 1997;55:353–361. doi: 10.1111/j.1753-4887.1997.tb01561.x. PubMed DOI

Neufeld G., Cohen T., Gengrinovitch S., Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 1999;13:9–22. doi: 10.1096/fasebj.13.1.9. PubMed DOI

Keisari Y., Braun L., Flescher E. The oxidative burst and related phenomena in mouse macrophages elicited by different sterile inflammatory stimuli. Immunobiology. 1983;165:78–89. doi: 10.1016/S0171-2985(83)80048-5. PubMed DOI

Ryter S.W., Kim H.P., Hoetzel A., Park J.W., Nakahira K., Wang X., Choi A.M. Mechanisms of cell death in oxidative stress. Antioxid. Redox Signal. 2007;9:49–89. doi: 10.1089/ars.2007.9.49. PubMed DOI

Azad M., Chen Y., Gibson S.B. Regulation of Autophagy by Reactive Oxygen Species (ROS): Implications for Cancer Progression and Treatment. Antioxidants Redox Signal. 2009;11:777–790. doi: 10.1089/ars.2008.2270. PubMed DOI

Cooke M.S., Evans M.D., Dizdaroglu M., Lunec J. Oxidative DNA damage: Mechanisms, mutation, and disease. FASEB J. 2003;17:1195–1214. doi: 10.1096/fj.02-0752rev. PubMed DOI

Nissanka N., Moraes C.T. Mitochondrial DNA damage and reactive oxygen species in neurodegenerative disease. FEBS Lett. 2018;592:728–742. doi: 10.1002/1873-3468.12956. PubMed DOI PMC

Stadtman E.R. Protein Oxidation in Aging and Age-Related Diseases. Ann. N. Y. Acad. Sci. 2001;928:22–38. doi: 10.1111/j.1749-6632.2001.tb05632.x. PubMed DOI

McCall M.R., Frei B. Can antioxidant vitamins materially reduce oxidative damage in humans? Free Radic. Biol. Med. 1999;26:1034–1053. doi: 10.1016/S0891-5849(98)00302-5. PubMed DOI

Kirsch M., De Groot H. NAD(P)H, a directly operating antioxidant? FASEB J. 2001;15:1569–1574. doi: 10.1096/fj.00-0823hyp. PubMed DOI

Lu J., Holmgren A. The thioredoxin antioxidant system. Free Radic. Biol. Med. 2014;66:75–87. doi: 10.1016/j.freeradbiomed.2013.07.036. PubMed DOI

Landis G.N., Tower J. Superoxide dismutase evolution and life span regulation. Mech. Ageing Dev. 2005;126:365–379. doi: 10.1016/j.mad.2004.08.012. PubMed DOI

Matés J.M., Pérez-Gómez C., De Castro I.N. Antioxidant enzymes and human diseases. Clin. Biochem. 1999;32:595–603. doi: 10.1016/S0009-9120(99)00075-2. PubMed DOI

Yadav A., Mishra P.C. Modeling the activity of glutathione as a hydroxyl radical scavenger considering its neutral non-zwitterionic form. J. Mol. Model. 2013;19:767–777. doi: 10.1007/s00894-012-1601-2. PubMed DOI

Winterbourn C.C., Metodiewa D. Reactivity of biologically important thiol compounds with superoxide and hydrogen peroxide. Free Radic. Biol. Med. 1999;27:322–328. doi: 10.1016/S0891-5849(99)00051-9. PubMed DOI

Forman H.J., Zhang H., Rinna A. Glutathione: Overview of its protective roles, measurement, and biosynthesis. Mol. Asp. Med. 2009;30:1–12. doi: 10.1016/j.mam.2008.08.006. PubMed DOI PMC

Kelner M.J., Bagnell R., Welch K.J. Thioureas react with superoxide radicals to yield a sulfhydryl compound. Explanation for protective effect against paraquat. J. Biol. Chem. 1990;265:1306–1311. doi: 10.1016/S0021-9258(19)40014-8. PubMed DOI

Azad G., Tomar R.S. Ebselen, a promising antioxidant drug: Mechanisms of action and targets of biological pathways. Mol. Biol. Rep. 2014;41:4865–4879. doi: 10.1007/s11033-014-3417-x. PubMed DOI

Zhang L., Zhou L., Du J., Li M., Qian C., Cheng Y., Peng Y., Xie J., Wang N. Induction of Apoptosis in Human Multiple Myeloma Cell Lines by Ebselen via Enhancing the Endogenous Reactive Oxygen Species Production. BioMed Res. Int. 2014;2014:696107. doi: 10.1155/2014/696107. PubMed DOI PMC

Halliwell B. Drug antioxidant effects. A basis for drug selection? Drugs. 1991;42:569–605. doi: 10.2165/00003495-199142040-00003. PubMed DOI PMC

Sunitha K., Hemshekhar M., Thushara R.M., Santhosh S., Yariswamy M., Kemparaju K., Girish K.S. N-Acetylcysteine amide: A derivative to fulfill the promises of N-Acetylcysteine. Free Radic. Res. 2013;47:357–367. doi: 10.3109/10715762.2013.781595. PubMed DOI

Valko M., Rhodes C.J., Moncol J., Izakovic M., Mazur M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem. Biol. Interact. 2006;160:1–40. doi: 10.1016/j.cbi.2005.12.009. PubMed DOI

White K., Bruckner J.V., Guess W.L. Toxicological Studies of 2-Mercaptoethanol. J. Pharm. Sci. 1973;62:237–241. doi: 10.1002/jps.2600620211. PubMed DOI

Held K.D., Melder D.C. Toxicity of the Sulfhydryl-Containing Radioprotector Dithiothreitol. Radiat. Res. 1987;112:544–554. doi: 10.2307/3577106. PubMed DOI

Bisby R., Ahmed S., Cundall R. Repair of amino acid radicals by a vitamin E analogue. Biochem. Biophys. Res. Commun. 1984;119:245–251. doi: 10.1016/0006-291X(84)91644-9. PubMed DOI

Davies M.J., Forni L.G., Willson R.L. Vitamin E analogue Trolox C. E.s.r. and pulse-radiolysis studies of free-radical reactions. Biochem. J. 1988;255:513–522. PubMed PMC

Gülçin I. Antioxidant activity of food constituents: An overview. Arch. Toxicol. 2012;86:345–391. doi: 10.1007/s00204-011-0774-2. PubMed DOI

Aruoma O.I., Halliwell B., Hoey B.M., Butler J. The antioxidant action of N-acetylcysteine: Its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid. Free Radic. Biol. Med. 1989;6:593–597. doi: 10.1016/0891-5849(89)90066-X. PubMed DOI

Gibson K.R., Neilson I.L., Barrett F., Winterburn T.J., Sharma S., MacRury S.M., Megson I.L. Evaluation of the Antioxidant Properties of N-acetylcysteine in Human Platelets: Prerequisite for Bioconversion to Glutathione for Antioxidant and Antiplatelet Activity. J. Cardiovasc. Pharmacol. 2009;54:319–326. doi: 10.1097/FJC.0b013e3181b6e77b. PubMed DOI

Aldini G., Altomare A.A., Baron G., Vistoli G., Carini M., Borsani L., Sergio F. N-Acetylcysteine as an antioxidant and disulphide breaking agent: The reasons why. Free Radic. Res. 2018;52:751–762. doi: 10.1080/10715762.2018.1468564. PubMed DOI

Zheng J., Lou J.R., Zhang X.-X., Benbrook D.M., Hanigan M.H., Lind S.E., Ding W.-Q. N-Acetylcysteine interacts with copper to generate hydrogen peroxide and selectively induce cancer cell death. Cancer Lett. 2010;298:186–194. doi: 10.1016/j.canlet.2010.07.003. PubMed DOI PMC

Mlejnek P., Dolezel P., Maier V., Kikalova K., Skoupa N. N-acetylcysteine dual and antagonistic effect on cadmium cytotoxicity in human leukemia cells. Environ. Toxicol. Pharmacol. 2019;71:103213. doi: 10.1016/j.etap.2019.103213. PubMed DOI

Mlejnek P., Dolezel P., Kriegova E., Pastvova N. N-acetylcysteine Can Induce Massive Oxidative Stress, Resulting in Cell Death with Apoptotic Features in Human Leukemia Cells. Int. J. Mol. Sci. 2021;22:12635. doi: 10.3390/ijms222312635. PubMed DOI PMC

Meister A., Anderson M.E. Glutathione. Annu. Rev. Biochem. 1983;52:711–760. doi: 10.1146/annurev.bi.52.070183.003431. PubMed DOI

Richman P.G., Meister A. Regulation of Gamma-Glutamyl-Cysteine Synthetase by Nonallosteric Feedback Inhibition by Glutathione. J. Biol. Chem. 1975;250:1422–1426. doi: 10.1016/S0021-9258(19)41830-9. PubMed DOI

Pompella A., Visvikis A., Paolicchi A., De Tata V., Casini A.F. The changing faces of glutathione, a cellular protagonist. Biochem. Pharmacol. 2003;66:1499–1503. doi: 10.1016/S0006-2952(03)00504-5. PubMed DOI

Phelps D.T., Deneke S.M., Daley D.L., Fanburg B.L. Elevation of Glutathione Levels in Bovine Pulmonary Artery Endothelial Cells by N-Acetylcysteine. Am. J. Respir. Cell Mol. Biol. 1992;7:293–299. doi: 10.1165/ajrcmb/7.3.293. PubMed DOI

Mlejnek P., Dolezel P. N-acetylcysteine prevents the geldanamycin cytotoxicity by forming geldanamycin–N-acetylcysteine adduct. Chem. Interactions. 2014;220:248–254. doi: 10.1016/j.cbi.2014.06.025. PubMed DOI

Ketterer B., Coles B., Meyer D.J. The role of glutathione in detoxication. Environ. Health Perspect. 1983;49:59–69. doi: 10.1289/ehp.834959. PubMed DOI PMC

LoPachin R.M., Gavin T. Molecular Mechanisms of Aldehyde Toxicity: A Chemical Perspective. Chem. Res. Toxicol. 2014;27:1081–1091. doi: 10.1021/tx5001046. PubMed DOI PMC

LoPachin R.M., Gavin T. Reactions of electrophiles with nucleophilic thiolate sites: Relevance to pathophysiological mechanisms and remediation. Free Radic. Res. 2016;50:195–205. doi: 10.3109/10715762.2015.1094184. PubMed DOI PMC

Jackson P.A., Widen J.C., Harki D.A., Brummond K.M. Covalent Modifiers: A Chemical Perspective on the Reactivity of α,β-Unsaturated Carbonyls with Thiols via Hetero-Michael Addition Reactions. J. Med. Chem. 2017;60:839–885. doi: 10.1021/acs.jmedchem.6b00788. PubMed DOI PMC

Pal S., Singh N., Ansari K.M. Toxicological effects of patulin mycotoxin on the mammalian system: An overview. Toxicol. Res. 2017;6:764–771. doi: 10.1039/c7tx00138j. PubMed DOI PMC

Speijers G., Franken M., van Leeuwen F. Subacute toxicity study of patulin in the rat: Effects on the kidney and the gastro-intestinal tract. Food Chem. Toxicol. 1988;26:23–30. doi: 10.1016/0278-6915(88)90037-3. PubMed DOI

Barhoumi R. Kinetic Analysis of the Chronology of Patulin- and Gossypol-Induced Cytotoxicityin Vitro. Fundam. Appl. Toxicol. 1996;30:290–297. doi: 10.1006/faat.1996.0067. PubMed DOI

Pfeiffer E., Gross K., Metzler M. Aneuploidogenic and clastogenic potential of the mycotoxins citrinin and patulin. Carcinogenesis. 1998;19:1313–1318. doi: 10.1093/carcin/19.7.1313. PubMed DOI

Fliege R., Metzler M. Electrophilic Properties of Patulin. N-Acetylcysteine and Glutathione Adducts. Chem. Res. Toxicol. 2000;13:373–381. doi: 10.1021/tx9901480. PubMed DOI

Zhang B., Peng X., Li G., Xu Y., Xia X., Wang Q. Oxidative stress is involved in Patulin induced apoptosis in HEK293 cells. Toxicon. 2015;94:1–7. doi: 10.1016/j.toxicon.2014.12.002. PubMed DOI

Boussabbeh M., Ben Salem I., Prola A., Guilbert A., Bacha H., Abid-Essefi S., Lemaire C. Patulin Induces Apoptosis through ROS-Mediated Endoplasmic Reticulum Stress Pathway. Toxicol. Sci. 2015;144:328–337. doi: 10.1093/toxsci/kfu319. PubMed DOI

Yang G., Bai Y., Wu X., Sun X., Sun M., Liu X., Yao X., Zhang C., Chu Q., Jiang L., et al. Patulin induced ROS-dependent autophagic cell death in Human Hepatoma G2 cells. Chem. Interact. 2018;288:24–31. doi: 10.1016/j.cbi.2018.03.018. PubMed DOI

Zhou S.-M., Jiang L.-P., Geng C.-Y., Cao J., Zhong L.-F. Patulin-induced genotoxicity and modulation of glutathione in HepG2 cells. Toxicon. 2009;53:584–586. doi: 10.1016/j.toxicon.2009.01.030. PubMed DOI

Song D., Gao Y., Wang R., Liu D., Zhao L., Jing Y. Down-regulation of c-FLIP, XIAP and Mcl-1 protein as well as depletion of reduced glutathione contribute to the apoptosis induction of glycyrrhenitic acid derivatives in leukemia cells. Cancer Biol. Ther. 2010;9:96–108. doi: 10.4161/cbt.9.2.10287. PubMed DOI

Mlejnek P., Dolezel P. Loss of mitochondrial transmembrane potential and glutathione depletion are not sufficient to account for induction of apoptosis by carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone in human leukemia K562 cells. Chem. Interact. 2015;239:100–110. doi: 10.1016/j.cbi.2015.06.033. PubMed DOI

Skoupa N., Dolezel P., Ruzickova E., Mlejnek P. Apoptosis Induced by the Curcumin Analogue EF-24 Is Neither Mediated by Oxidative Stress-Related Mechanisms nor Affected by Expression of Main Drug Transporters ABCB1 and ABCG2 in Human Leukemia Cells. Int. J. Mol. Sci. 2017;18:2289. doi: 10.3390/ijms18112289. PubMed DOI PMC

DeBoer C., Meulman P.A., Wnuk R.J., Peterson D.H. Geldanamycin a new antibiotic. J. Antibiot. 1970;23:442–447. doi: 10.7164/antibiotics.23.442. PubMed DOI

Uehara Y., Hori M., Takeuchi T., Umezawa H. Phenotypic change from transformed to normal induced by benzoquinonoid ansamycins accompanies inactivation of p60src in rat kidney cells infected with Rous sarcoma virus. Mol. Cell. Biol. 1986;6:2198–2206. doi: 10.1128/mcb.6.6.2198. PubMed DOI PMC

Whitesell L., Cook P. Stable and specific binding of heat shock protein 90 by geldanamycin disrupts glucocorticoid receptor function in intact cells. Mol. Endocrinol. 1996;10:705–712. doi: 10.1210/mend.10.6.8776730. PubMed DOI

Ochel H.J., Schulte T.W., Nguyen P., Trepel J., Neckers L. The benzoquinone ansamycin geldanamycin stimulates proteolytic degradation of focal adhesion kinase. Mol. Genet. Metab. 1999;66:24–30. doi: 10.1006/mgme.1998.2774. PubMed DOI

Holt S.E., Aisner D.L., Baur J., Tesmer V.M., Dy M., Ouellette M., Trager J.B., Morin G.B., Toft D.O., Shay J.W., et al. White Functional requirement of p23 and Hsp90 in telomerase complexes. Genes Dev. 1999;13:817–826. doi: 10.1101/gad.13.7.817. PubMed DOI PMC

Sakagami M., Morrison P., Welch W.J. Benzoquinoid ansamycins (herbimycin A and geldanamycin) interfere with the maturation of growth factor receptor tyrosine kinases. Cell Stress Chaperones. 1999;4:19–28. doi: 10.1379/1466-1268(1999)004<0019:BAHAAG>2.3.CO;2. PubMed DOI PMC

An W.G., Schulte T.W., Neckers L.M. The heat shock protein 90 antagonist geldanamycin alters chaperone association with p210 bcr-abl and v-src proteins before their degradation by the proteasome. Cell Growth Differ. 2000;11:355–360. PubMed

Benchekroun M.N., Myers C.E., Sinha B.K. Free radical formation by ansamycin benzoquinone in human breast tumor cells: Implications for cytotoxicity and resistance. Free Radic. Biol. Med. 1994;17:191–200. doi: 10.1016/0891-5849(94)90074-4. PubMed DOI

Clark C.B., Rane M.J., El Mehdi D., Miller C.J., Sachleben L.R., Gozal E. Role of oxidative stress in geldanamycin-induced cytotoxicity and disruption of Hsp90 signaling complex. Free Radic. Biol. Med. 2009;47:1440–1449. doi: 10.1016/j.freeradbiomed.2009.08.012. PubMed DOI PMC

Heytler P., Prichard W. A new class of uncoupling agent—Carbonyl cyanide phenylhydrazones. Biochem. Biophys. Res. Commun. 1962;7:272–275. doi: 10.1016/0006-291X(62)90189-4. PubMed DOI

Han Y.H., Kim S.H., Kim S.Z., Park W.H. Carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP) as an O2− generator induces apoptosis via the depletion of intracellular GSH contents in Calu-6 cells. Lung Cancer. 2009;63:201–209. doi: 10.1016/j.lungcan.2008.05.005. PubMed DOI

Han Y.H., Moon H.J., You B.R., Kim S.Z., Kim S.H., Park W.H. Effects of carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone on the growth inhibition in human pulmonary adenocarcinoma Calu-6 cells. Toxicology. 2009;265:101–107. doi: 10.1016/j.tox.2009.10.001. PubMed DOI

Han Y.H., Park W.H. Intracellular glutathione levels are involved in carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone-induced apoptosis in As4.1 juxtaglomerular cells. Int. J. Mol. Med. 2011;27:575–581. PubMed

Drobnica L., Sturdik E. The reactions of carbonyl cyanide phenylhydrazones with thiols. Biochim. Biophys. Acta. 1979;585:462–476. doi: 10.1016/0304-4165(79)90091-6. PubMed DOI

Adams B.K., Ferstl E.M., Davis M.C., Herold M., Kurtkaya S., Camalier R.F., Hollingshead M.G., Kaur G., Sausville E.A., Rickles F.R., et al. Synthesis and biological evaluation of novel curcumin analogs as anti-cancer and anti-angiogenesis agents. Bioorg. Med. Chem. 2004;12:3871–3883. doi: 10.1016/j.bmc.2004.05.006. PubMed DOI

Kasinski A.L., Du Y., Thomas S.L., Zhao J., Sun S.Y., Khuri F.R., Wang C.Y., Shoji M., Sun A., Snyder J.P., et al. Inhibition of IkappaB kinase-nuclear factor-kappaB signaling pathway by 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24), a novel monoketone analog of curcumin. Mol. Pharmacol. 2008;74:654–661. doi: 10.1124/mol.108.046201. PubMed DOI PMC

Subramaniam D., May R., Sureban S.M., Lee K.B., George R., Kuppusamy P., Ramanujam R.P., Hideg K., Dieckgraefe B.K., Houchen C.W., et al. Diphenyl Difluoroketone: A Curcumin Derivative with Potent In vivo Anticancer Activity. Cancer Res. 2008;68:1962–1969. doi: 10.1158/0008-5472.CAN-07-6011. PubMed DOI

Liu H., Liang Y., Wang L., Tian L., Song R., Han T., Pan S., Liu L. In Vivo and In Vitro Suppression of Hepatocellular Carcinoma by EF24, a Curcumin Analog. PLoS ONE. 2012;7:e48075. doi: 10.1371/journal.pone.0048075. PubMed DOI PMC

Yang C.H., Yue J., Sims M., Pfeffer L.M. The Curcumin Analog EF24 Targets NF-κB and miRNA-21, and Has Potent Anticancer Activity In Vitro and In Vivo. PLoS ONE. 2013;8:e71130. doi: 10.1371/journal.pone.0071130. PubMed DOI PMC

Selvendiran K., Tong L., Vishwanath S., Bratasz A., Trigg N.J., Kutala V.K., Hideg K., Kuppusamy P. EF24 induces G2/M arrest and apoptosis in cisplatin-resistant human ovarian cancer cells by increasing PTEN expression. J. Biol. Chem. 2007;282:28609–28618. doi: 10.1074/jbc.M703796200. PubMed DOI PMC

Thomas S.L., Zhong D., Zhou W., Malik S., Liotta D., Snyder J.P., Hamel E., Giannakakou P. EF24, a novel curcumin analog, disrupts the microtubule cytoskeleton and inhibits HIF-1. Cell Cycle. 2008;7:2409–2417. doi: 10.4161/cc.6410. PubMed DOI PMC

Adams B.K., Cai J., Armstrong J., Herold M., Lu Y.J., Sun A., Snyder J.P., Liotta D.C., Jones D.P., Shoji M. EF-24, a novel synthetic curcumin analog, induces apoptosis in cancer cells via a redox-dependent mechanism. Anticancer Drugs. 2005;16:263–275. doi: 10.1097/00001813-200503000-00005. PubMed DOI

Sun A., Lu Y.J., Hu H., Shoji M., Liotta D.C., Snyder J.P. Curcumin analog cytotoxicity against breast cancer cells: Exploitation of a redox-dependent mechanism. Bioorg. Med. Chem. Lett. 2009;19:6627–6631. doi: 10.1016/j.bmcl.2009.10.023. PubMed DOI PMC

Chen W., Zou P., Zhao Z., Chen X., Fan X., Vinothkumar R., Cui R., Wu F., Zhang Q., Liang G., et al. Synergistic antitumor activity of rapamycin and EF24 via increasing ROS for the treatment of gastric cancer. Redox Biol. 2016;10:78–89. doi: 10.1016/j.redox.2016.09.006. PubMed DOI PMC

Zou P., Xia Y., Chen W., Chen X., Ying S., Feng Z., Chen T., Ye Q., Wang Z., Qiu C., et al. EF24 induces ROS-mediated apoptosis via targeting thioredoxin reductase 1 in gastric cancer cells. Oncotarget. 2016;7:18050–18064. doi: 10.18632/oncotarget.7633. PubMed DOI PMC

He G., Feng C., Vinothkumar R., Chen W., Dai X., Chen X., Ye Q., Qiu C., Zhou H., Wang Y., et al. Curcumin analog EF24 induces apoptosis via ROS-dependent mitochondrial dysfunction in human colorectal cancer cells. Cancer Chemother. Pharmacol. 2016;78:1151–1161. doi: 10.1007/s00280-016-3172-x. PubMed DOI

Zhang Y., Talalay P. Anticarcinogenic activities of organic isothiocyanates: Chemistry and mechanisms. Cancer Res. 1994;54((Suppl. 7)):1976s–1981s. PubMed

Shukla S., Gupta S. Dietary agents in the chemoprevention of prostate cancer. Nutr Cancer. 2005;53:18–32. doi: 10.1207/s15327914nc5301_3. PubMed DOI

Park H.S., Han M.H., Kim G.Y., Moon S.K., Kim W.J., Hwang H.J., Park K.Y., Choi Y.H. Sulforaphane induces reactive oxygen species-mediated mitotic arrest and subsequent apoptosis in human bladder cancer 5637 cells. Food Chem. Toxicol. 2014;64:157–165. doi: 10.1016/j.fct.2013.11.034. PubMed DOI

Lin J.F., Tsai T.F., Yang S.C., Lin Y.C., Chen H.E., Chou K.Y., Hwang T.I. Benzyl isothiocyanate induces reactive oxygen species-initiated autophagy and apoptosis in human prostate cancer cells. Oncotarget. 2017;8:20220–20234. doi: 10.18632/oncotarget.15643. PubMed DOI PMC

Shoaib S., Tufail S., Sherwani M.A., Yusuf N., Islam N. Phenethyl Isothiocyanate Induces Apoptosis Through ROS Generation and Caspase-3 Activation in Cervical Cancer Cells. Front Pharmacol. 2021;12:673103. doi: 10.3389/fphar.2021.673103. PubMed DOI PMC

Podhradský D., Drobnica L., Kristian P. Reactions of cysteine, its derivatives, glutathione coenzyme A, and dihydrolipoic acid with isothiocyanates. Experientia. 1979;35:154–155. doi: 10.1007/BF01920581. PubMed DOI

Mi L., Sirajuddin P., Gan N., Wang X. A cautionary note on using N-acetylcysteine as an antagonist to assess isothiocyanate-induced reactive oxygen species-mediated apoptosis. Anal Biochem. 2010;405:269–271. doi: 10.1016/j.ab.2010.06.015. PubMed DOI PMC

Georgiou-Siafis S.K., Samiotaki M.K., Demopoulos V.J., Panayotou G., Tsiftsoglou A.S. Formation of novel N-acetylcysteine-hemin adducts abrogates hemin-induced cytotoxicity and suppresses the NRF2-driven stress response in human pro-erythroid K562 cells. Eur. J. Pharmacol. 2020;880:173077. doi: 10.1016/j.ejphar.2020.173077. PubMed DOI

Laird M.D., Wakade C., Alleyne C.H., Jr., Dhandapani K.M. Hemin-induced necroptosis involves glutathione depletion in mouse astrocytes. Free Radic. Biol. Med. 2008;45:1103–1114. doi: 10.1016/j.freeradbiomed.2008.07.003. PubMed DOI

Kim K.-Y., Rhim T., Choi I., Kim S.-S. N-Acetylcysteine Induces Cell Cycle Arrest in Hepatic Stellate Cells through Its Reducing Activity. J. Biol. Chem. 2001;276:40591–40598. doi: 10.1074/jbc.M100975200. PubMed DOI

Cotgreave I.A. N-acetylcysteine: Pharmacological considerations and experimental and clinical applications. Adv. Pharmacol. 1997;38:205–227. PubMed

LeBel C.P., Ischiropoulos H., Bondy S.C. Evaluation of the probe 2’,7’-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem. Res. Toxicol. 1992;5:227–231. doi: 10.1021/tx00026a012. PubMed DOI

Parvez S., Long M.J.C., Poganik J.R., Aye Y. Redox Signaling by Reactive Electrophiles and Oxidants. Chem. Rev. 2018;118:8798–8888. doi: 10.1021/acs.chemrev.7b00698. PubMed DOI PMC

Sauerland M., Mertes R., Morozzi C., Eggler A.L., Gamon L.F., Davies M.J. Kinetic assessment of Michael addition reactions of alpha, beta-unsaturated carbonyl compounds to amino acid and protein thiols. Free Radic. Biol. Med. 2021;169:1–11. doi: 10.1016/j.freeradbiomed.2021.03.040. PubMed DOI

Krenske E.H., Petter R.C., Houk K.N. Kinetics and Thermodynamics of Reversible Thiol Additions to Mono- and Diactivated Michael Acceptors: Implications for the Design of Drugs That Bind Covalently to Cysteines. J. Org. Chem. 2016;81:11726–11733. doi: 10.1021/acs.joc.6b02188. PubMed DOI

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...