Suppression of tumor necrosis factor-induced cell death by inhibitor of apoptosis c-IAP2 is under NF-κB control

Chu, Zhi-Liang; McKinsey, Timothy A.; Liu, Lily; Gentry, Jennifer J.; Malim, Michael H.; Ballard, Dean W.

doi:10.1073/pnas.94.19.10057

Cited by 825 publications

(607 citation statements)

References 45 publications

Supporting

Mentioning

581

Contrasting

Unclassified

Order By: Relevance

“…Additionally we, Wang et al (1996), and others (Arsura et al, 1996;Beg and Baltimore, 1996;Liu et al, 1996;Van Antwerp et al, 1996;Chu et al, 1997), have shown that NF-kB suppresses apoptosis initiated by tumor necrosis factor, chemotherapy or radiation.…”

Section: Introductionmentioning

confidence: 76%

Selective activation of NF-κB subunits in human breast cancer: potential roles for NF-κB2/p52 and for Bcl-3

et al. 2000

View full text Add to dashboard Cite

Members of the NF-kB/Rel transcription factor family have been shown recently to be required for cellular transformation by oncogenic Ras and by other oncoproteins and to suppress transformation-associated apoptosis. Furthermore, NF-kB has been shown to be activated by several oncoproteins including HER2/Neu, a receptor tyrosine kinase often expressed in human breast cancer. Human breast cancer cell lines, human breast tumors and normal adjacent tissue were analysed by gel mobility shift assay, immunoblotting of nuclear extracts and immunohistochemistry for activation of NF-kB. Furthermore, RNA levels for NF-kB-activated genes were analysed in order to determine if NF-kB is functionally active in human breast cancer. Our data indicate that the p65/RelA subunit of NF-kB is activated (i.e., nuclear) in breast cancer cell lines. However, breast tumors exhibit an absence or low level of nuclear p65/RelA but show activated c-Rel, p50 and p52 as compared to nontumorigenic adjacent tissue. Additionally, the IkB homolog Bcl-3, which functions to stimulate transcription with p50 or p52, was also activated in breast tumors. There was no apparent correlation between estrogen receptor status and levels of nuclear NF-kB complexes. Transcripts of NF-kB-regulated genes were found elevated in breast tumors, as compared to adjacent normal tissue, indicating functional NF-kB activity. These data suggest a potential role for a subset of NF-kB and IkB family proteins, particularly NF-kB/p52 and Bcl-3, in human breast cancer. Additionally, the activation of functional NF-kB in these tumors likely involves a signal transduction pathway distinct from that utilized by cytokines.

show abstract

Section: Introductionmentioning

confidence: 76%

Selective activation of NF-κB subunits in human breast cancer: potential roles for NF-κB2/p52 and for Bcl-3

et al. 2000

View full text Add to dashboard Cite

show abstract

“…NFkB can also induce anti-apoptotic genes such as cellular FLICE inhibitory protein (c-FLIP) and cIAPs that prevent cell death. [38][39][40] RIP1 can also mediate TNF-induced activation of the mitogen-activated protein kinases (MAPKs) ERK, p38 and JNK and, interestingly, although the kinase activity of RIP1 is dispensable for activating NFkB, p38 and JNK, it is required to stimulate ERK activity. 41 Although ubiquitinated RIP1 serves to promote downstream activation of NFkB and gene expression that drives inflammation and protects cells from death by apoptosis, 42 NFkB can also induce the deubiquitinating enzymes CYLD Figure 1 The RIP kinase family.…”

Section: Rip1 and Tnf Signalling: Inflammation Versus Apoptosismentioning

confidence: 99%

RIP kinases: key decision makers in cell death and innate immunity

et al. 2014

View full text Add to dashboard Cite

“…Because the constitutive expression of the proteins Bfl-1, xIAP, cFLIP, BclXL, Bcl-2, and survivin has been implicated in cell survival and anti-apoptosis [25][26][27][28][29][30][31][32][33], we examined the effect of guggulsterone on the constitutive expression of these genes. Guggulsterone suppressed the expression of these genes in a time-dependent manner ( Fig.…”

Section: Guggulsterone Inhibits Anti-apoptotic Gene Productsmentioning

confidence: 99%

Guggulsterone inhibits tumor cell proliferation, induces S-phase arrest, and promotes apoptosis through activation of c-Jun N-terminal kinase, suppression of Akt pathway, and downregulation of antiapoptotic gene products

Shishodia

Sethi

Ahn

et al. 2007

Biochemical Pharmacology

121

119

View full text Add to dashboard Cite

Guggulsterone is a plant polyphenol traditionally used to treat obesity, diabetes, hyperlipidemia, atherosclerosis, and osteoarthritis, possibly through an anti-inflammatory mechanism. Whether this steroid has any role in cancer is not known. In this study, we found that guggulsterone inhibits the proliferation of wide variety of human tumor cell types including leukemia, head and neck carcinoma, multiple myeloma, lung carcinoma, melanoma, breast carcinoma, and ovarian carcinoma. Guggulsterone also inhibited the proliferation of drug-resistant cancer cells (e.g., gleevac-resistant leukemia, dexamethasone-resistant multiple myeloma, and doxorubicin-resistant breast cancer cells). Guggulsterone suppressed the proliferation of cells through inhibition of DNA synthesis, producing cell cycle arrest in S-phase, and this arrest correlated with a decrease in the levels of cyclin D1 and cdc2 and a concomitant increase in the levels of cyclin-dependent kinase inhibitor p21 and, p27. Guggulsterone induced apoptosis as indicated by increase in the number of Annexin V-and TUNEL-positive cells, through the down-regulation of anti-apoptototic products. The apoptosis induced by guggulsterone was also indicated by the activation of caspase 8, bid cleavage, cytochrome c release, caspase 9 activation, caspase 3 activation, and PARP cleavage. The apoptotic effects of guggulsterone were preceded by activation of JNK and down-regulation of Akt activity. JNK was needed for guggulsterone-induced apoptosis, inasmuch as inhibition of JNK by pharmacological inhibitors or by genetic deletion of MKK4 (activator of JNK) abolished the activity. Overall, our results indicate that guggulsterone can inhibit cell proliferation and induce apoptosis through the activation of JNK, suppression of Akt, and down-regulation of anti-apoptotic protein expression.

show abstract

Suppression of tumor necrosis factor-induced cell death by inhibitor of apoptosis c-IAP2 is under NF-κB control

Abstract: ABSTRACT

Cited by 825 publications

References 45 publications

Selective activation of NF-κB subunits in human breast cancer: potential roles for NF-κB2/p52 and for Bcl-3

Selective activation of NF-κB subunits in human breast cancer: potential roles for NF-κB2/p52 and for Bcl-3

RIP kinases: key decision makers in cell death and innate immunity

Guggulsterone inhibits tumor cell proliferation, induces S-phase arrest, and promotes apoptosis through activation of c-Jun N-terminal kinase, suppression of Akt pathway, and downregulation of antiapoptotic gene products

Contact Info

Product

Resources

About