Insights into the mechanism of natural terpenoids as NF-kB inhibitors: an overview on their anticancer potential

Jain, Hasmukh; Dhingra, Naveen; Narsinghani, Tamanna; Sharma, Rajesh

doi:10.31768/2312-8852.2016.38(3):158-168

Cited by 36 publications

(26 citation statements)

References 51 publications

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“…It was reported that several key genes in the inflammatory process such as NF- κ B provide a mechanistic link between inflammation and cancer [45–48]. Activation of TLRs and TNFR leads to NF- κ B activation and induced the expression of many proinflammatory molecules including NO synthase 2 (iNOS) [49, 50].…”

Section: Discussionmentioning

confidence: 99%

All-Trans Retinoic Acid Modulates TLR4/NF-κB Signaling Pathway Targeting TNF-αand Nitric Oxide Synthase 2 Expression in Colonic Mucosa during Ulcerative Colitis and Colitis Associated Cancer

Rafa

Benkhelifa

Ait-Younes

et al. 2017

Mediators of Inflammation

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Colitis associated cancer (CAC) is the colorectal cancer (CRC) subtype that is associated with bowel disease such as ulcerative colitis (UC). The data on role of NF-κB signaling in development and progression of CAC were derived from preclinical studies, whereas data from human are rare. The aim of this work was to study the contribution of NF-κB pathway during UC and CAC, as well as the immunomodulatory effect of all-trans retinoic acid (AtRA). We analyzed the expression of NOS2, TNF-α, TLR4, and NF-κB, in colonic mucosa. We also studied NO/TNF-α modulation by LPS in colonic mucosa pretreated with AtRA. A marked increase in TLR4, NF-κB, TNF-α, and NOS2 expression was reported in colonic mucosa. The relationship between LPS/TLR4 and TNF-α/NO production, as well as the role of NF-κB signaling, was confirmed by ex vivo experiments and the role of LPS/TLR4 in NOS2/TNF-α induction through NF-κB pathway was suggested. AtRA downregulates NOS2 and TNF-α expression. Collectively, our study indicates that AtRA modulates in situ LPS/TLR4/NF-κB signaling pathway targeting NOS2 and TNF-α expression. Therefore, we suggest that AtRA has a potential value in new strategies to improve the current therapy, as well as in the clinical prevention of CAC development and progression.

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Section: Discussionmentioning

confidence: 99%

All-Trans Retinoic Acid Modulates TLR4/NF-κB Signaling Pathway Targeting TNF-αand Nitric Oxide Synthase 2 Expression in Colonic Mucosa during Ulcerative Colitis and Colitis Associated Cancer

Rafa

Benkhelifa

Ait-Younes

et al. 2017

Mediators of Inflammation

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“…NF-κB activity is mediated by numerous signaling pathways such as mitogen-activated protein kinases (MAPKs) and IκB kinase (IKK). The upregulation of IKK complexes phosphorylate the IκB subunits of NF-κB/IκB and subsequently activate the NF-κB (Jain et al, 2016 ). IKK activity is triggered during aging by NF-κB (Kim et al, 2002 ), which further modulates the p38 MAPK, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinases (JNKs) pathways that modulate the NF-κB-dependent transcriptional activity during the inflammatory reaction.…”

Section: Molecular Inflammation Involved During Agingmentioning

confidence: 99%

Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases

et al. 2018

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Aging is the progressive loss of organ and tissue function over time. Growing older is positively linked to cognitive and biological degeneration such as physical frailty, psychological impairment, and cognitive decline. Oxidative stress is considered as an imbalance between pro- and antioxidant species, which results in molecular and cellular damage. Oxidative stress plays a crucial role in the development of age-related diseases. Emerging research evidence has suggested that antioxidant can control the autoxidation by interrupting the propagation of free radicals or by inhibiting the formation of free radicals and subsequently reduce oxidative stress, improve immune function, and increase healthy longevity. Indeed, oxidation damage is highly dependent on the inherited or acquired defects in enzymes involved in the redox-mediated signaling pathways. Therefore, the role of molecules with antioxidant activity that promote healthy aging and counteract oxidative stress is worth to discuss further. Of particular interest in this article, we highlighted the molecular mechanisms of antioxidants involved in the prevention of age-related diseases. Taken together, a better understanding of the role of antioxidants involved in redox modulation of inflammation would provide a useful approach for potential interventions, and subsequently promoting healthy longevity.

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“…A plethora of compounds consisting of small molecules, biologics, inhibitory peptides, and many other different types of bioactive molecules have been identified as inhibitors of NF-κB and categorized into different groups based on the stage of NF-κB activation at which they exert their inhibitory effects [ 111 , 112 , 113 , 114 ]. These groups include agents that act at various steps of NF-κB signaling at (i) upstream of IKK, (ii) directly affecting the IKK complex or IκB phosphorylation, (iii) ubiquitination or proteasomal degradation of IκB, (iv) nuclear translocation of NF-κB, (v) NF-κB DNA binding, and (vi) NF-κB-directed gene transactivation.…”

Section: Inhibitors Of Nf-κb Function and Selected Pharmacologicalmentioning

confidence: 99%

Evidence for the Involvement of the Master Transcription Factor NF-κB in Cancer Initiation and Progression

et al. 2018

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Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is responsible for the regulation of a large number of genes that are involved in important physiological processes, including survival, inflammation, and immune responses. At the same time, this transcription factor can control the expression of a plethora of genes that promote tumor cell proliferation, survival, metastasis, inflammation, invasion, and angiogenesis. The aberrant activation of this transcription factor has been observed in several types of cancer and is known to contribute to aggressive tumor growth and resistance to therapeutic treatment. Although NF-κB has been identified to be a major contributor to cancer initiation and development, there is evidence revealing its role in tumor suppression. This review briefly highlights the major mechanisms of NF-κB activation, the role of NF-κB in tumor promotion and suppression, as well as a few important pharmacological strategies that have been developed to modulate NF-κB function.

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Insights into the mechanism of natural terpenoids as NF-kB inhibitors: an overview on their anticancer potential

Cited by 36 publications

References 51 publications

All-Trans Retinoic Acid Modulates TLR4/NF-κB Signaling Pathway Targeting TNF-αand Nitric Oxide Synthase 2 Expression in Colonic Mucosa during Ulcerative Colitis and Colitis Associated Cancer

All-Trans Retinoic Acid Modulates TLR4/NF-κB Signaling Pathway Targeting TNF-αand Nitric Oxide Synthase 2 Expression in Colonic Mucosa during Ulcerative Colitis and Colitis Associated Cancer

Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases

Evidence for the Involvement of the Master Transcription Factor NF-κB in Cancer Initiation and Progression

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