Transcriptional regulation of bcl-2 by nuclear factor κB and its significance in prostate cancer

Catz, Sergio D.; Johnson, Jack

doi:10.1038/sj.onc.1204926

Cited by 484 publications

(336 citation statements)

References 75 publications

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“…It is also responsible for the transcription of Th1-response cytokines such as IFN-c and IL-12p70. NF-jB is sequestered by the inactive form of IjB in the cytosol, which prevents its activity in the promoter regions of a variety of pro-survival genes including IAP, Bcl-2, Bcl-x L , FLIP and Gadd45b in the nucleus [44,45]. Our data showing that the active cytosolic form of IjB is down-regulated, with accumulation of its inactive form, is consistent with the increased apoptotic and impaired maturation phenotype observed in db/db DC.…”

Section: Discussionmentioning

confidence: 99%

Involvement of leptin signaling in the survival and maturation of bone marrow‐derived dendritic cells

et al. 2006

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Previous studies demonstrated that lymphocyte development is impaired in leptin receptor (Ob-R)-deficient db/db mice. However, it remains unclear whether or not leptin signaling plays a physiological role in dendritic cell (DC) development and function. In this study, we first detected Ob-R expression in murine DC. Using db/db mice at a pre-diabetic stage, we demonstrate that the total number of DC generated from bone marrow (BM) cultures is significantly lower than in WT controls. Similarly, selective blockade of leptin with a soluble mouse Ob-R chimera (Ob-R:Fc) inhibited DC generation in wild-type BM cultures. The reduced DC yield in db/db BM culture was attributed to significantly increased apoptosis, which was associated with dysregulated expression of Bcl-2 family genes. Moreover, db/db DC displayed markedly reduced expression of co-stimulatory molecules and a Th2-type cytokine profile, with a poor capacity to stimulate allogeneic T cell proliferation. Consistent with their impaired DC phenotype and function, db/db DC showed significantly down-regulated activities of the PI3K/Akt pathway as well as STAT-3 and IjB-a. In conclusion, our findings demonstrate the involvement of leptin signaling in DC survival and maturation.See accompanying commentary: http://dx

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Section: Discussionmentioning

confidence: 99%

Involvement of leptin signaling in the survival and maturation of bone marrow‐derived dendritic cells

et al. 2006

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“…In non-simulated cells, NF-kB is inactivated by binding to IkB in the cytoplasm. On apoptotic stimulation, however, proteolytic degradation of IkB unmasks a nuclear target sequence within NF-kB and leads to its translocation to the nucleus, where it induces transcription of various genes, including antiapoptotic Bcl-2 and Bcl-XL (Baldwin, 1996;Pahl, 1999;Catz and Johnson, 2001;Bharti and Aggarwal, 2002;Beinke and Ley, 2004;Panwalkar et al, 2004). The p50/RelA (p65) heterodimer, 'specifically' known as NF-kB, is the most common dimer, and the most important transcriptional regulator playing a major antiapoptotic role in anticancer drug-treated mammalian cells (Baeuerle and Henkel, 1994;Ghosh et al, 1998;Panwalkar et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of hRFI inhibits 5-fluorouracil-induced apoptosis in colorectal cancer cells via activation of NF-κB and upregulation of BCL-2 and BCL-XL

et al. 2006

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Resistance to apoptosis is one of the important determinants of resistance to 5-fluorouracil (5-FU) in colorectal cancer cells. Human Ring-Finger homologous to Inhibitor of apoptosis protein type (hRFI) is a newly discovered gene that has been shown to inhibit death receptormediated apoptosis in colorectal cancer cells. However, the molecular mechanism of the inhibition of apoptosis is presently unknown. In order to investigate the molecular function of hRFI in the regulation of 5-FU-induced apoptosis in colorectal cancer cells, HCT116 cells were stably transfected with hRFI or LacZ as a control. hRFI overexpression resulted in cellular resistance to 5-FU through an inhibition of the mitochondrial apoptotic pathway and specific upregulation of Bcl-2 and Bcl-XL. Futhermore, hRFI overexpression resulted in the activation of nuclear factor-jB (NF-jB). Inhibition of NF-jB effectively reversed the resistance to apoptosis as well as the upregulation of Bcl-2 and Bcl-XL in the hRFI transfectant, indicating that the activation of NF-jB is the key mechanism for all these findings. Overexpression of hRFI in SW480 and COLO320 colorectal cancer cells similarly resulted in resistance to 5-FU with the activation of NF-jB and upregulation of Bcl-2 and Bcl-XL. hRFI might be a novel therapeutic target for gene therapy in colorectal cancer.

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“…Because NF-κB regulates the expression of antiapoptotic proteins such as IAP1 [33], Bcl-2 [34], and Bcl-xL [35], we examined whether curcumin can modulate the expression of these antiapoptotic gene products and, if so, whether GSH can block the effect of curcumin. Western blot analysis showed that TNF induced these antiapoptotic proteins, whereas curcumin significantly suppressed them (Fig.…”

Section: Glutathione Inhibits Curcumin-mediated Suppression Of Tnf-inmentioning

confidence: 99%

Role of pro-oxidants and antioxidants in the anti-inflammatory and apoptotic effects of curcumin (diferuloylmethane)

Sandur

Ichikawa

Pandey

et al. 2007

Free Radical Biology and Medicine

275

172

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Extensive research within last half a century has indicated that curcumin (diferuloylmethane), a yellow pigment in curry powder, exhibits antioxidant, anti-inflammatory and proapoptotic activities. Whether anti-inflammatory and proapoptotic activities assigned to curcumin, are mediated through its antioxidant mechanism was investigated. We found that TNF-mediated NF-κB activation was inhibited by curcumin; and glutathione reversed the inhibition. Similarly, suppression of TNFinduced AKT activation by curcumin, was also abrogated by glutathione. The reducing agent also counteracted the inhibitory effect of curcumin on TNF-induced NF-κB regulated antiapoptotic (Bcl-2, Bcl-xL, IAP1), proliferative (cyclin D1) and proinflammatory (COX-2, iNOS and MMP-9) gene products. The suppression of TNF-induced AP-1 activation by curcumin was also reversed by glutathione. Also, the direct proapoptotic effects of curcumin were inhibited by glutathione and potentiated by depletion of intracellular glutathione by buthionine sulfoximine. Moreover, curcumin induced the production of reactive oxygen species (ROS) and modulated the intracellular GSH levels. Quenchers of hydroxyl radicals, however, were ineffective in inhibiting curcumin mediated NF-κB suppression. Further, N-acetylcysteine partially reversed the effect of curcumin. Based on these results we conclude that curcumin mediate its apoptotic and anti-inflammatory activities through modulation of the redox status of the cell.

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Transcriptional regulation of bcl-2 by nuclear factor κB and its significance in prostate cancer

Cited by 484 publications

References 75 publications

Involvement of leptin signaling in the survival and maturation of bone marrow‐derived dendritic cells

Involvement of leptin signaling in the survival and maturation of bone marrow‐derived dendritic cells

Overexpression of hRFI inhibits 5-fluorouracil-induced apoptosis in colorectal cancer cells via activation of NF-κB and upregulation of BCL-2 and BCL-XL

Role of pro-oxidants and antioxidants in the anti-inflammatory and apoptotic effects of curcumin (diferuloylmethane)

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