Combinatorial effect of non-steroidal anti-inflammatory drugs and NF-kappaB inhibitors in ovarian cancer therapy

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dc.contributor.authorZerbini, Luiz Fen_ZA
dc.contributor.authorTamura, Rodrigo Een_ZA
dc.contributor.authorCorrea, Ricardo Gen_ZA
dc.contributor.authorCzibere, Akosen_ZA
dc.contributor.authorCordeiro, Jasonen_ZA
dc.contributor.authorBhasin, Manojen_ZA
dc.contributor.authorSimabuco, Fernando Men_ZA
dc.contributor.authorWang, Yihongen_ZA
dc.contributor.authorGu, Xuesongen_ZA
dc.contributor.authorLi, Linglinen_ZA
dc.date.accessioned2016-01-11T06:55:13Z
dc.date.available2016-01-11T06:55:13Z
dc.date.issued2011en_ZA
dc.description.abstractSeveral epidemiological studies have correlated the use of non-steroidal anti-inflammatory drugs (NSAID) with reduced risk of ovarian cancer, the most lethal gynecological cancer, diagnosed usually in late stages of the disease. We have previously established that the pro-apoptotic cytokine melanoma differentiation associated gene-7/Interleukin-24 ( mda -7/IL-24) is a crucial mediator of NSAID-induced apoptosis in prostate, breast, renal and stomach cancer cells. In this report we evaluated various structurally different NSAIDs for their efficacies to induce apoptosis and mda -7/IL-24 expression in ovarian cancer cells. While several NSAIDs induced apoptosis, Sulindac Sulfide and Diclofenac most potently induced apoptosis and reduced tumor growth. A combination of these agents results in a synergistic effect. Furthermore, mda -7/IL-24 induction by NSAIDs is essential for programmed cell death, since inhibition of mda -7/IL-24 by small interfering RNA abrogates apoptosis. mda -7/IL-24 activation leads to upregulation of growth arrest and DNA damage inducible (GADD) 45 α and γ and JNK activation. The NF-κB family of transcription factors has been implicated in ovarian cancer development. We previously established NF-κB/IκB signaling as an essential step for cell survival in cancer cells and hypothesized that targeting NF-κB could potentiate NSAID-mediated apoptosis induction in ovarian cancer cells. Indeed, combining NSAID treatment with NF-κB inhibitors led to enhanced apoptosis induction. Our results indicate that inhibition of NF-κB in combination with activation of mda -7/IL-24 expression may lead to a new combinatorial therapy for ovarian cancer.en_ZA
dc.identifier.apacitationZerbini, L. F., Tamura, R. E., Correa, R. G., Czibere, A., Cordeiro, J., Bhasin, M., ... Li, L. (2011). Combinatorial effect of non-steroidal anti-inflammatory drugs and NF-kappaB inhibitors in ovarian cancer therapy. <i>PLoS One</i>, http://hdl.handle.net/11427/16295en_ZA
dc.identifier.chicagocitationZerbini, Luiz F, Rodrigo E Tamura, Ricardo G Correa, Akos Czibere, Jason Cordeiro, Manoj Bhasin, Fernando M Simabuco, Yihong Wang, Xuesong Gu, and Linglin Li "Combinatorial effect of non-steroidal anti-inflammatory drugs and NF-kappaB inhibitors in ovarian cancer therapy." <i>PLoS One</i> (2011) http://hdl.handle.net/11427/16295en_ZA
dc.identifier.citationZerbini, L. F., Tamura, R. E., Correa, R. G., Czibere, A., Cordeiro, J., Bhasin, M., ... & Sarkar, D. (2011). Combinatorial effect of non-steroidal anti-inflammatory drugs and NF-kappaB inhibitors in ovarian cancer therapy. PLoS One, 6(9), e24285. doi:10.1371/journal.pone.0024285en_ZA
dc.identifier.ris TY - Journal Article AU - Zerbini, Luiz F AU - Tamura, Rodrigo E AU - Correa, Ricardo G AU - Czibere, Akos AU - Cordeiro, Jason AU - Bhasin, Manoj AU - Simabuco, Fernando M AU - Wang, Yihong AU - Gu, Xuesong AU - Li, Linglin AB - Several epidemiological studies have correlated the use of non-steroidal anti-inflammatory drugs (NSAID) with reduced risk of ovarian cancer, the most lethal gynecological cancer, diagnosed usually in late stages of the disease. We have previously established that the pro-apoptotic cytokine melanoma differentiation associated gene-7/Interleukin-24 ( mda -7/IL-24) is a crucial mediator of NSAID-induced apoptosis in prostate, breast, renal and stomach cancer cells. In this report we evaluated various structurally different NSAIDs for their efficacies to induce apoptosis and mda -7/IL-24 expression in ovarian cancer cells. While several NSAIDs induced apoptosis, Sulindac Sulfide and Diclofenac most potently induced apoptosis and reduced tumor growth. A combination of these agents results in a synergistic effect. Furthermore, mda -7/IL-24 induction by NSAIDs is essential for programmed cell death, since inhibition of mda -7/IL-24 by small interfering RNA abrogates apoptosis. mda -7/IL-24 activation leads to upregulation of growth arrest and DNA damage inducible (GADD) 45 α and γ and JNK activation. The NF-κB family of transcription factors has been implicated in ovarian cancer development. We previously established NF-κB/IκB signaling as an essential step for cell survival in cancer cells and hypothesized that targeting NF-κB could potentiate NSAID-mediated apoptosis induction in ovarian cancer cells. Indeed, combining NSAID treatment with NF-κB inhibitors led to enhanced apoptosis induction. Our results indicate that inhibition of NF-κB in combination with activation of mda -7/IL-24 expression may lead to a new combinatorial therapy for ovarian cancer. DA - 2011 DB - OpenUCT DO - 10.1371/journal.pone.0024285 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2011 T1 - Combinatorial effect of non-steroidal anti-inflammatory drugs and NF-kappaB inhibitors in ovarian cancer therapy TI - Combinatorial effect of non-steroidal anti-inflammatory drugs and NF-kappaB inhibitors in ovarian cancer therapy UR - http://hdl.handle.net/11427/16295 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16295
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0024285
dc.identifier.vancouvercitationZerbini LF, Tamura RE, Correa RG, Czibere A, Cordeiro J, Bhasin M, et al. Combinatorial effect of non-steroidal anti-inflammatory drugs and NF-kappaB inhibitors in ovarian cancer therapy. PLoS One. 2011; http://hdl.handle.net/11427/16295.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Medical Biochemistryen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2011 Zerbini et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherApoptosisen_ZA
dc.subject.otherNSAIDsen_ZA
dc.subject.otherOvarian canceren_ZA
dc.subject.otherCancer treatmenten_ZA
dc.subject.otherSulfidesen_ZA
dc.subject.otherSmall interfering RNAsen_ZA
dc.subject.otherGene expressionen_ZA
dc.subject.otherDieten_ZA
dc.titleCombinatorial effect of non-steroidal anti-inflammatory drugs and NF-kappaB inhibitors in ovarian cancer therapyen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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