Nuclear factor-kappa B links carcinogenic and chemopreventive agents

Lau, Keith K

doi:10.2741/e6

Cited by 21 publications

(21 citation statements)

References 44 publications

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“…These results suggested that NF-kB inhibition may specifically target liver TICs. To test this hypothesis, we utilized an effective IKK inhibitor curcumin, known to block NF-kB signaling [30], and 5 liver cancer cell lines including one primary HCC cell line referred to as Pitts1. The results showed that a 3-day treatment with 25 μM curcumin reduced cell viability (not shown) and significantly increased cell death (Fig.…”

Section: Resultsmentioning

confidence: 99%

Curcumin effectively inhibits oncogenic NF-κB signaling and restrains stemness features in liver cancer

Marquardt

Gómez–Quiroz

Camacho

et al. 2015

Journal of Hepatology

259

163

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Background & Aims The cancer stem cells (CSCs) have important therapeutic implications for multi-resistant cancers including hepatocellular carcinoma (HCC). Among the key pathways frequently activated in liver CSCs is NF-kB signaling. Methods We evaluated the CSCs-depleting potential of NF-kB inhibition in liver cancer achieved by the IKK inhibitor curcumin, RNAi and specific peptide SN50. The effects on CSCs were assessed by analysis of Side Population (SP), sphere formation and tumorigenicity. Molecular changes were determined by RT-qPCR, global gene expression microarray, EMSA, and Western blotting. Results HCC cell lines exposed to curcumin exhibited differential responses to curcumin and were classified as sensitive and resistant. In sensitive lines, curcumin-mediated induction of cell death was directly related to the extent of NF-kB inhibition. The treatment also led to a selective CSC-depletion as evidenced by a reduced SP size, decreased sphere formation, down-regulation of CSC markers and suppressed tumorigenicity. Similarly, NF-kB inhibition by SN50 and siRNA against p65 suppressed tumor cell growth. In contrast, curcumin-resistant cells displayed a paradoxical increase in proliferation and expression of CSC markers. Mechanistically, an important component of the CSC-depleting activity of curcumin could be attributed to a NF-kB-mediated HDAC inhibition. Co-administration of the class I/II HDAC inhibitor trichostatine sensitized resistant cells to curcumin. Further, integration of a predictive signature of curcumin sensitivity with human HCC database indicated that HCCs with poor prognosis and progenitor features are most likely to benefit from NF-kB inhibition. Conclusions These results demonstrate that blocking NF-kB can specifically target CSC populations and suggest a potential for combined inhibition of NF-kB and HDAC signaling for treatment of liver cancer patients with poor prognosis.

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Section: Resultsmentioning

confidence: 99%

Curcumin effectively inhibits oncogenic NF-κB signaling and restrains stemness features in liver cancer

Marquardt

Gómez–Quiroz

Camacho

et al. 2015

Journal of Hepatology

259

163

View full text Add to dashboard Cite

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“…Several studies have shown that curcuminoid compounds can act as free-radical scavengers by reducing lipid peroxidation mediated by free radicals [16][17][18]. One of the most important discoveries in this field has been the curcumin-mediated suppression of nuclear factor kB (NF-kB), which has a key role in triggering the inflammatory cascade in most chronic illnesses [19][20][21]. Importantly, NF-kB-dependent gene products also prevent apoptosis and promote cell proliferation, invasion and angiogenesis [22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

The role of curcumin in liver diseases

Buonomo¹,

Scotto²,

Nappa³

et al. 2019

aoms

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A b s t r a c tChronic liver diseases are a major medical problem worldwide. Despite the availability of etiologic-specific treatments for several liver diseases, no drug or medication is available for the regression of hepatic fibrosis and cirrhosis. Curcumin is a natural compound extractable from turmeric. Several studies have uncovered its role in the modulation of biological mechanisms involved in liver injury. The best known biological effect of curcumin is the interaction with different pathways involved in the development of liver fibrosis, as shown in both in vitro and in vivo models of chronic liver injury. In pre-clinical studies, curcumin was also effective in decreasing alcohol-, glucose-and hepatitis C virus (HCV)-related liver injury, as well as HCV replication in hepatocytes. These data make curcumin a potential therapeutic agent for regression of fibrosis and cirrhosis, especially in the setting of HCV infection that can be easily eradicated thanks to the availability of several direct-acting antivirals.

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“…Chemotherapeutic agents and gamma irradiation activate NF-κB and lead to chemoresistance and radioresistance (Ahn et al 2008). Thus, suppression of these proinflammatory pathways may provide opportunities for both prevention and treatment of cancer (Aggarwal 2006Ralhan et al 2009). …”

Section: Cancer Is More Common In Western/developed Countriesmentioning

confidence: 99%

Genome-Based Multi-targeting of Cancer: Hype or Hope?

Singh

Tyagi

Raman

et al. 2014

Multi-Targeted Approach to Treatment of Cancer

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Cancer is primarily an "old-age disease" that has an "age-old" history. The overall incidence of cancer is much higher in Western countries than in Eastern countries for reasons that are not understood. Almost three million studies published to date indicate that cancer is a hyperproliferative disorder that arises from dysregulation of multiple cell signaling pathways. The cancer genome landscape indicates that approximately 140 genes and 12 cell signaling pathways drive almost all types of cancers. "Targeted therapy," a buzz word in cancer treatment for the past two decades, has provided antibodies as well as small-molecule inhibitors of ligands, receptors, kinases, proteasomes, and transcription factors. In most cases, such drugs have been highly ineffective, with overall increases in survival of only few days; furthermore, in most cases, those who need these drugs cannot afford them. Natural products, in contrast, are often more effective against cancer and are very affordable; these untargeted or multitargeted products have been used from the very beginning of human history and are the roots for almost 70 % of modern drugs. The past, present, and future of preventing and treating cancer, usually a disease of lifestyle, is discussed in this mini review.

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Nuclear factor-kappa B links carcinogenic and chemopreventive agents

Cited by 21 publications

References 44 publications

Curcumin effectively inhibits oncogenic NF-κB signaling and restrains stemness features in liver cancer

Curcumin effectively inhibits oncogenic NF-κB signaling and restrains stemness features in liver cancer

The role of curcumin in liver diseases

Genome-Based Multi-targeting of Cancer: Hype or Hope?

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