Colon carcinogenesis: Learning from NF-κB and AP-1

Vaiopoulos, Aristeidis G.; Papachroni, Katerina K.; Papavassiliou, Athanasios G.

doi:10.1016/j.biocel.2010.03.018

Cited by 70 publications

(66 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Since no additional inhibitory effects of [6]-gingerol were seen in combination with the inhibitors of ERK1/2 or JNK, we believe that no other additional factors up-regulated by PMA in SW-480 cells are affected by [6]-gingerol. Stimulation of MEK-ERK1/2 pathway by growth factors and induction of both ERK1/2 and JNK pathways by oncogenic proteins like Src and Ras, leading to the activation of their downstream targets, like AP-1, have been found crucial in the development of colon cancer [45], [46]. Inhibition of the constituents of MAP kinase pathway has long been recognized as ideal approach to arrest the progression of colon cancer [46].There are reports on other natural compounds like epicatechin gallate, curcumin, silibinin and red ginseng of inducing apoptosis in colon cancer cells via inhibition of MAP kinases [15], [47], [48], [49].…”

Section: Discussionmentioning

confidence: 99%

“…Stimulation of MEK-ERK1/2 pathway by growth factors and induction of both ERK1/2 and JNK pathways by oncogenic proteins like Src and Ras, leading to the activation of their downstream targets, like AP-1, have been found crucial in the development of colon cancer [45], [46]. Inhibition of the constituents of MAP kinase pathway has long been recognized as ideal approach to arrest the progression of colon cancer [46].There are reports on other natural compounds like epicatechin gallate, curcumin, silibinin and red ginseng of inducing apoptosis in colon cancer cells via inhibition of MAP kinases [15], [47], [48], [49]. [6]-gingerol was previously shown to inhibit the phosphorylation of ERK1/2, JNK and p38 MAP kinases in mouse skin cancer cell lines, hepatocarcinoma cells and pancreatic cancer cells [28], [34], [36], [50].…”

Section: Discussionmentioning

confidence: 99%

“…There are increasing evidence which establish the role of transcription factors like NF-kappB and AP-1 in tumourigenesis, progression, invasion and metastasis of cancer of colon epithelium [46]. In colon cancer, NF-kappaB plays an anti-apoptosis role by many means like, by inhibiting the ROS pathways, by inhibiting JNK cascade and by inducing the expression of anti-apoptotic genes Bcl-2, Bcl-x and cIAPs [51], [52].…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

[6]-Gingerol Induces Caspase-Dependent Apoptosis and Prevents PMA-Induced Proliferation in Colon Cancer Cells by Inhibiting MAPK/AP-1 Signaling

et al. 2014

View full text Add to dashboard Cite

We report mechanism-based evidence for the anticancer and chemopreventive efficacy of [6]-gingerol, the major active principle of the medicinal plant, Ginger (Zingiber officinale), in colon cancer cells. The compound was evaluated in two human colon cancer cell lines for its cytotoxic effect and the most sensitive cell line, SW-480, was selected for the mechanistic evaluation of its anticancer and chemopreventive efficacy. The non-toxic nature of [6]-gingerol was confirmed by viability assays on rapidly dividing normal mouse colon cells. [6]-gingerol inhibited cell proliferation and induced apoptosis as evidenced by externalization of phosphatidyl serine in SW-480, while the normal colon cells were unaffected. Sensitivity to [6]-gingerol in SW-480 cells was associated with activation of caspases 8, 9, 3 &7 and cleavage of PARP, which attests induction of apoptotic cell death. Mechanistically, [6]-gingerol down-regulated Phorbol Myristate Acetate (PMA) induced phosphorylation of ERK1/2 and JNK MAP kinases and activation of AP-1 transcription factor, but had only little effects on phosphorylation of p38 MAP kinase and activation of NF-kappa B. Additionally, it complemented the inhibitors of either ERK1/2 or JNK MAP kinase in bringing down the PMA-induced cell proliferation in SW-480 cells. We report the inhibition of ERK1/2/JNK/AP-1 pathway as a possible mechanism behind the anticancer as well as chemopreventive efficacy of [6]-gingerol against colon cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

[6]-Gingerol Induces Caspase-Dependent Apoptosis and Prevents PMA-Induced Proliferation in Colon Cancer Cells by Inhibiting MAPK/AP-1 Signaling

et al. 2014

View full text Add to dashboard Cite

show abstract

“…It has also been demonstrated that NF-κB plays an important role in the control of cell proliferation, survival and invasion as well as angiogenesis 32) . We previously demonstrated that the activation of NF-κB p65 is a process mediated by multiple receptors, although the activation of NF-κB p65 by LPS and anti-β2GPI/β2GPI is primarily mediated by TLR4 8) .…”

Section: Discussionmentioning

confidence: 99%

Involvement of TLR4 in Oxidized LDL/β2GPI/Anti-β2GPI-Induced Transformation of Macrophages to Foam Cells

Zhang

Xie

Zhou

et al. 2014

JAT

View full text Add to dashboard Cite

Aim: It has been reported that oxidized low-density lipoprotein (oxLDL) forms a stable and non-dissociable complex with β2-glycoprotein I (β2GPI) and that IgG anti-β2GPI autoantibodies are able to recognize this complex, thus facilitating macrophage-derived foam cell formation in patients with antiphospholipid syndrome (APS). However, the immunopathological mechanisms of oxLDL/β2GPI complexes in promoting foam cell formation are not fully understood. In this study, we examined the role of toll-like receptor 4 (TLR4) in the oxLDL/β2GPI/anti-β2GPI complex-induced transformation of mouse peritoneal macrophages to foam cells.

show abstract

“…Members of the activating protein 1 (AP-1) and nuclear factor-B (NF-B) families of transcription factors control many essential physiological and pathological processes including inflammation, immune responses, host-defense, and cancer (for review, see Ghosh and Hayden, 2008;Peng, 2008;Vaiopoulos et al, 2010). Because these transcription factors are key regulators of the inducible expression of many proinflammatory mediators, their inhibition by small-molecule compounds represents an area of interest for new drug de-velopment.…”

Section: Introductionmentioning

confidence: 99%

Identification and Characterization of a Novel Class of c-Jun N-terminal Kinase Inhibitors

et al. 2012

View full text Add to dashboard Cite

In efforts to identify novel small molecules with antiinflammatory properties, we discovered a unique series of tetracyclic indenoquinoxaline derivatives that inhibited lipopolysaccharide (LPS)-induced nuclear factor-B/activating protein 1 activation. Compound IQ-1 (11H-indeno[1,2-b]quinoxalin-11-one oxime) was found to be a potent, noncytotoxic inhibitor of pro-inflammatory cytokine [interleukin (IL)-1␣, IL-1␤, IL-6, IL-10, tumor necrosis factor (TNF)-␣, interferon-␥, and granulocyte-macrophage colony-stimulating factor] and nitric oxide production by human and murine monocyte/macrophages. Three additional potent inhibitors of cytokine production were identified through further screening of IQ-1 analogs. The sodium salt of IQ-1 inhibited LPS-induced TNF-␣ and IL-6 production in MonoMac-6 cells with IC 50 values of 0.25 and 0.61 M, respectively. Screening of 131 protein kinases revealed that derivative IQ-3 [11H-indeno[1,2-b]quinoxalin-11-one-O-(2-furoyl)oxime]was a specific inhibitor of the c-Jun N-terminal kinase (JNK) family, with preference for JNK3. This compound, as well as IQ-1 and three additional oxime indenoquinoxalines, were found to be high-affinity JNK inhibitors with nanomolar binding affinity and ability to inhibit c-Jun phosphorylation. Furthermore, docking studies showed that hydrogen bonding interactions of the active indenoquinoxalines with Asn152, Gln155, and Met149 of JNK3 played an important role in enzyme binding activity. Finally, we showed that the sodium salt of IQ-1 had favorable pharmacokinetics and inhibited the ovalbumin-induced CD4 ϩ T-cell immune response in a murine delayed-type hypersensitivity model in vivo. We conclude that compounds with an indenoquinoxaline nucleus can serve as specific small-molecule modulators for mechanistic studies of JNKs as well as a potential leads for the development of anti-inflammatory drugs.

show abstract

Colon carcinogenesis: Learning from NF-κB and AP-1

Cited by 70 publications

References 28 publications

[6]-Gingerol Induces Caspase-Dependent Apoptosis and Prevents PMA-Induced Proliferation in Colon Cancer Cells by Inhibiting MAPK/AP-1 Signaling

[6]-Gingerol Induces Caspase-Dependent Apoptosis and Prevents PMA-Induced Proliferation in Colon Cancer Cells by Inhibiting MAPK/AP-1 Signaling

Involvement of TLR4 in Oxidized LDL/β2GPI/Anti-β2GPI-Induced Transformation of Macrophages to Foam Cells

Identification and Characterization of a Novel Class of c-Jun N-terminal Kinase Inhibitors

Contact Info

Product

Resources

About