Abstract
Oxidative stress regulates NF-κB signaling pathway and induces the transcription of genes related to apoptosis and cell proliferation. Due to its crucial role in the pathogenesis of diseases caused by oxidative damage, it is believed that NF-κB is a promising target for treatment of diseases resulting from ROS, like cancer. There is a plethora of bioactive natural compounds, isolated from plants and organisms that exhibit anti-tumor activity against various types of cancer through modulation of ROS/NF-κB signaling. Some of these compounds belong to large natural product families like terpenoids, alkaloids, steroids and saponins.
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References
Baldwin AS (1996) The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol 14:649–683
Bonizzi G, Karin M (2004) The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol 25:280–288
Cao Y, Wei W, Zhang N, Yu Q et al (2015) Oridonin stabilizes retinoic acid receptor alpha through ROS-activated NF-κB signaling. BMC Cancer 15:248
Chang W, Li RN, Wang HR, Liu JR et al (2017) Withaferin A induces oxidative stress-mediated apoptosis and DNA damage in Oral cancer cells. Front Physiol 8:634
Cheng CL, Chao WT, Li YH, Ou YC et al (2018) Escin induces apoptosis in human bladder cancer cells: an in vitro and in vivo study. Eur J Pharmacol 840:79–88
Chung SS, Vadgama JV (2015) Curcumin and epigallocatechin gallate inhibit the cancer stem cell phenotype via down-regulation of STAT3–NFκB signaling. Anticancer Res 35(1):39–46
D’Anneo A, Carlisi D, Lauricella M, Puleio R et al (2013) Parthenolide generates reactive oxygen species and autophagy in MDA-MB231 cells. A soluble parthenolide analogue inhibits tumour growth and metastasis in a xenograft model of breast cancer. Cell Death Dis 4(10):e891
De Jager TL, Cockrell AE, Du Plessis SS (2017) Ultraviolet light induced generation of reactive oxygen species. Ultraviolet light in human health, diseases and environment. Adv Exp Med Biol 996:15–23
Di W, Khan M, Rasul A, Sun M et al (2014) Isoalantolactone inhibits constitutive NF-κB activation and induces reactive oxygen species-mediated apoptosis in osteosarcoma U2OS cells through mitochondrial dysfunction. Oncol Rep 32:1585–1593
Ding Y, Xue Q, Liu S, Hu K et al (2020) Identification of Parthenolide dimers as activators of pyruvate kinase M2 in xenograft of glioblastoma Multiforme in vivo. J Med Chem. https://doi.org/10.1021/acs.jmedchem.9b01328
Ghosh S, May MJ, Kopp EB (1998) NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol 16:225–260
Gloire G, Piette J (2009) Redox regulation of nuclear post-translational modifications during NF-κB activation. Antioxid Redox Signal 11:2209–2222
He H, Zang LH, Feng YS, Chen LX, Kang N, Tashiro S, Onodera S, Qiu F, Ikejima T (2013) Physalin A induces apoptosis via p53-Noxa-mediated ROS generation, and autophagy plays a protective role against apoptosis through p38-NF-κB survival pathway in A375-S2 cells. J Ethnopharmacol 148(2):544–555
Hehner SP, Hofmann TG, Dröge W, Schmitz ML (1999) The antiinflammatory sesquiterpene lactone parthenolide inhibits NF-kappa B by targeting the I kappa B kinase complex. J Immunol 163(10):5617–5623
Herscovitch M, Comb W, Ennis T, Coleman K et al (2008) Intermolecular disulfide bond formation in the NEMO dimer requires Cys54 and Cys347. Biochem Biophys Res Commun 367:103–108
Hewson QD, Lovat PE, Corazzari M, Catterall JB, Redfern CP (2005) The NF-kappaB pathway mediates fenretinide-induced apoptosis in SH-SY5Y neuroblastoma cells. Apoptosis 10:493–498
Hirota K, Murata M, Sachi Y et al (1999) Distinct roles of thioredoxin in the cytoplasm and in the nucleus. A two-step mechanism of redox regulation of transcription factor NF-kappaB. J Biol Chem 274:27891–27897
Hoffmann R, von Schwarzenberg K, López-Antón N, Rudy A et al (2011) Helenalin bypasses Bcl-2-mediated cell death resistance by inhibiting NF-κB and promoting reactive oxygen species generation. Biochem Pharmacol 82:453–463
Hu H, Li K, Wang X, Liu Y et al (2012) Set9, NF-κB and microRNA-21 mediate berberine-induced apoptosis of human multiple myeloma cells. Acta Pharmacol Sin 34(1):157–166
Hu W, Chen SS, Zhang JL et al (2014) Dihydroartemisinin induces autophagy by suppressing NF-κB activation. Cancer Lett 343:239–248
Huang M, **n W (2018) Matrine inhibiting pancreatic cells epithelial-mesenchymal transition and invasion through ROS/NF-κB/MMPs pathway. Life Sci 192:55–61
Jamaluddin M, Wang S, Boldogh I, Tian B, Brasier AR (2007) TNF-alpha-induced NF-kappaB/RelA Ser(276) phosphorylation and enhanceosome formation is mediated by an ROS-dependent PKAc pathway. Cell Signal 19:1419–1433
Jeong CH, Ryu H, Kim DH, Cheng WN et al (2019a) Piperlongumine induces cell cycle arrest via reactive oxygen species accumulation and IKKβ suppression in human breast cancer cells. Antioxidants (Basel) 8(11):553
Jeong Y, Lim JW, Kim H (2019b) Lycopene inhibits reactive oxygen species-mediated NF-κB signaling and induces apoptosis in pancreatic cancer cells. Nutrients 11(4):762
Ji Q, Ding YH, Sun Y, Zhang Y et al (2016) Antineoplastic effects and mechanisms of micheliolide in acute myelogenous leukemia stem cells. Oncotarget 7:65012–65023
** L, Zhang B, Hua S, Ji M et al (2018) Glycyrrhetinic acid derivatives containing aminophosphonate ester species as multidrug resistance reversers that block the NF-κB pathway and cell proliferation. Bioorg Med Chem Lett 28:3700–3707
Kil IS, Kim SY, Park JW (2008) Glutathionylation regulates IkappaB. Biochem Biophys Res Commun 373:169–173
Kim EA, Sung EG, Song IH, Kim JY et al (2019) Neferine-induced apoptosis is dependent on the suppression of Bcl-2 expression via downregulation of p65 in renal cancer cells. Acta Biochim Biophys Sin Shanghai 51(7):734–742
Klaunig JE, Kamendulis LM (2004) The role of oxidative stress in carcinogenesis. Annu Rev Pharmacol Toxicol 44:239–267
Kwok BH, Koh B, Ndubuisi MI, Elofsson M, Crews CM (2001) The anti-inflammatory natural product parthenolide from the medicinal herb feverfew directly binds to and inhibits IkappaB kinase. Chem Biol 8(8):759–766
Lau ST, Lin ZX, Leung PS (2010) Role of reactive oxygen species in brucein D-mediated p38-mitogen-activated protein kinase and nuclear factor-kappaB signalling pathways in human pancreatic adenocarcinoma cells. Br J Cancer 102:583–593
Lee KY, Chang W, Qiu D, Kao PN, Rosen GD (1999) PG490 (triptolide) cooperates with tumor necrosis factor-alpha to induce apoptosis in tumor cells. J Biol Chem 274(19):13451–13455
Li Q, Engelhardt JF (2006) Interleukin-1beta induction of NFkappaB is partially regulated by H2O2-mediated activation of NFkappaB-inducing kinase. J Biol Chem 281:1495–1505
Li B, Zhao J, Wang CZ, Searle J et al (2011) Ginsenoside Rh2 induces apoptosis and paraptosis-like cell death in colorectal cancer cells through activation of p53. Cancer Lett 301:185–192
Li J, Li S, Guo J, Li Q et al (2018a) Natural product Micheliolide (MCL) irreversibly activates pyruvate kinase M2 and suppresses leukemia. J Med Chem 61(9):4155–4164
Li X, Qu Z, **g S, Li X et al (2018b) Dioscin-6′-O-acetate inhibits lung cancer cell proliferation via inducing cell cycle arrest and caspase-dependent apoptosis. Phytomedicine 53:124–133
Li Q, Chen L, Dong Z, Zhao Y et al (2019) Piperlongumine analogue L50377 induces pyroptosis via ROS mediated NF-κB suppression in non-small-cell lung cancer. Chem Biol Interact 313:108820–108826
Liao G, Zhang M, Harhaj EW, Sun SC (2004) Regulation of the NFkappaB-inducing kinase by tumor necrosis factor receptorassociated factor 3-induced degradation. J Biol Chem 279:26243–26250
Liu S, Wu D, Li L, Sun X et al (2014) NF-κB activation was involved in reactive oxygen species-mediated apoptosis and autophagy in 1-oxoeudesm-11(13)-eno-12,8α-lactone-treated human lung cancer cells. Arch Pharm Res 37:1039–1052
Liu X, Li Y, Ma Q, Wang Y, Song AL (2019) Withaferin-A inhibits growth of drug-resistant breast carcinoma by inducing apoptosis and autophagy, endogenous reactive oxygen species (ROS) production, and inhibition of cell migration and nuclear factor kappa B (Nf-κB)/mammalian target of rapamycin (m-TOR) Signalling pathway. Med Sci Monit 25:6855–6863
Ma B, Zhu J, Zhao A, Zhang J et al (2018) Raddeanin A, a natural triterpenoid saponin compound, exerts anticancer effect on human osteosarcoma via the ROS/JNK and NF-κB signal pathway. Toxicol Appl Pharmacol 353:87–101
Malik F, Kumar A, Bhushan S, Khan S et al (2007) Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic cell death of human myeloid leukemia HL-60 cells by a dietary compound withaferin A with concomitant protection by N-acetyl cysteine. Apoptosis 12(11):2115–2133
Markesbery WR, Lovell MA (2007) Damage to lipids, proteins, DNA, and RNA in mild cognitive impairment. Arch Neurol 64(7):954–956
Marquardt JU et al (2015) Curcumin effectively inhibits oncogenic NF-κB signaling and restrains stemness features in liver cancer. J Hepatol 63(3):661–669
Matthews JR, Kaszubska W, Turcatti G, Wells TN, Hay RT (1993) Role of cysteine62 in DNA recognition by the P50 subunit of NF-kappa B. Nucleic Acids Res 21:1727–1734
Morgan MJ, Liu Z (2010) Crosstalk of reactive oxygen species and NF-κB signaling. Cell Res 21(1):103–115
Morgan MJ, Kim YS, Liu Z (2008) TNFα and reactive oxygen species in necrotic cell death. Cell Res 18(3):343–349
Palozza P, Serini S, Torsello A, Di Nicuolo F, Piccioni E, Ubaldi V, Pioli C, Wolf FI, Calviello G (2003) Beta-carotene regulates NF-kappaB DNA-binding activity by a redox mechanism in human and colon adenocarcinoma cells. J Nutr 133:381–388
Poornima P, Kumar VB, Weng CF, Padma VV (2014) Doxorubicin induced apoptosis was potentiated by neferine in human lung adenocarcima, A549 cells. Food Chem Toxicol 68:87–98
Reynaert NL, van der Vliet A, Guala AS, McGovern T et al (2006) Dynamic redox control of NF-kappaB through glutaredoxin-regulated S-glutathionylation of inhibitory kappaB kinase beta. Proc Natl Sci USA 103:13086–13091
Schoonbroodt S, Ferreira V, Best-Belpomme M, Boelaert JR et al (2000) Crucial role of the amino-terminal tyrosine residue 42 and the carboxyl-terminal PEST domain of I kappa B alpha in NF-kappa B activation by an oxidative stress. J Immunol 164:4292–4300
Sen R, Baltimore D (1986) Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell 47:921–928
Shanmugam R, Kusumanchi P, Appaiah H, Cheng L et al (2010) A water soluble parthenolide analog suppresses in vivo tumor growth of two tobacco-associated cancers, lung and bladder cancer, by targeting NF-κB and generating reactive oxygen species. Int J Cancer 128(10):2481–2494
Takada Y, Kobayashi Y, Aggarwal BB (2005) Evodiamine abolishes constitutive and inducible NF-κB activation by inhibiting IκBα kinase activation, thereby suppressing NF-κB-regulated antiapoptotic and metastatic gene expression, up-regulating apoptosis, and inhibiting invasion. J Biol Chem 280(17):17203–17212
Tang F, Tang G, **ang J, Dai Q, Rosner MR, Lin A (2002) The absence of NF-κB-mediated inhibition of c-Jun N-terminal kinase activation contributes to tumor necrosis factor alpha-induced apoptosis. Mol Cell Biol 22(24):8571–8579
Wang J, Zhao B, Zhang W, Wu X et al (2010) Mycoepoxydiene, a fungal polyketide, induces cell cycle arrest at the G2/M phase and apoptosis in HeLa cells. Bioorg Med Chem Lett 20(23):7054–7058
Wang CZ, Li B, Wen XD, Zhang Z et al (2013) Paraptosis and NF-κB activation are associated with protopanaxadiol-induced cancer chemoprevention. BMC Complement Altern Med 13:2
Wang Y, Zhang B, Liu W, Dai Y et al (2016) Noninvasive bioluminescence imaging of the dynamics of sanguinarine induced apoptosis via activation of reactive oxygen species. Oncotarget 7(16):22355–22367
Wang C, Gu W, Zhang Y, Ji Y et al (2017a) Nicotine promotes cervical carcinoma cell line HeLa migration and invasion by activating PI3k/Akt/NF-κB pathway in vitro. Exp Toxicol Pathol 69(6):402–407
Wang YS, Lin Y, Li H, Li Y et al (2017b) The identification of molecular target of (20S) ginsenoside Rh2 for its anti-cancer activity. Sci Rep 7(1):12408
Wu HY, Yang FL, Li LH, Rao YK et al (2018) Ergosterol peroxide from marine fungus Phoma sp. induces ROS-dependent apoptosis and autophagy in human lung adenocarcinoma cells. Sci Rep 8:17956–17970
**ao G, Fong A, Sun SC (2004) Induction of p100 processing by NF-kappaB-inducing kinase involves docking IkappaB kinase alpha (IKKalpha) to p100 and IKKalpha-mediated phosphorylation. J Biol Chem 279:30099–30105
**e JH, Lai ZQ, Zheng XH, **an YF et al (2019) Apoptosis induced by bruceine D in human non-small-cell lung cancer cells involves mitochondrial ROS-mediated death signaling. Int J Mol Med 44:2015–2026
Xu B, Guo X, Mathew S, Armesilla AL et al (2010) Triptolide simultaneously induces reactive oxygen species, inhibits NF-kappaB activity and sensitizes 5-fluorouracil in colorectal cancer cell lines. Cancer Lett 291:200–208
Xu N, Hua Z, Ba G, Zhang S et al (2019) The anti-tumor growth effect of a novel agent DMAMCL in rhabdomyosarcoma in vitro and in vivo. J Exp Clin Cancer Res 38:118
Yamamoto Y, Gaynor RB (2004) IkappaB kinases: key regulators of the NF-kappaB pathway. Trends Biochem Sci 29:72–79
Yang L, Zhang XY, Li K, Li AP et al (2019) Protopanaxadiol inhibits epithelial-mesenchymal transition of hepatocellular carcinoma by targeting STAT3 pathway. Cell Death Dis 10(9):630
Yao J, Duan D, Song ZL, Zhang J, Fang J (2020) Sanguinarine as a new chemical entity of thioredoxin reductase inhibitor to elicit oxidative stress and promote tumor cell apoptosis. Free Radic Biol Med S0891-5849(19):32389–32385
Youn H, Jeong JC, Jeong YS, Kim E-J, Um SJ (2013) Quercetin potentiates apoptosis by inhibiting nuclear factor-kappaB signaling in H460 lung cancer cells. Biol Pharm Bull 36(6):944–951
Zhang Q, Chen W, Lv X, Weng Q et al (2019) Piperlongumine, a novel TrxR1 inhibitor, induces apoptosis in hepatocellular carcinoma cells by ROS-mediated ER stress. Front Pharmacol 10:1180. eCollection 2019
Zheng T, **ao H, Shen Y, Zhang X et al (2019) Anticancer effects of curzerenone against drug-resistant human lung carcinoma cells are mediated via programmed cell death, loss of mitochondrial membrane potential, ROS,and blocking the ERK/MAPK and NF-κB signaling pathway. JBUON 24(3):908–912
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Voura, M., Sflakidou, E., Sarli, V. (2022). Modulators of ROS/NF-κB Signaling in Cancer Therapy. In: Chakraborti, S. (eds) Handbook of Oxidative Stress in Cancer: Therapeutic Aspects. Springer, Singapore. https://doi.org/10.1007/978-981-16-5422-0_169
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DOI: https://doi.org/10.1007/978-981-16-5422-0_169
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