Transcription Factors as Targets for Cancer Therapy: AP-1 a Potential Therapeutic Target

Leaner, Virna D.; Donninger, Howard; Birrer, Michael J.

doi:10.2174/157339407780126665

Cited by 14 publications

(9 citation statements)

References 76 publications

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“…Generally, carcinogenesis is considered to have three stages including initiation, promotion, and progression and metastasis. Although mutations of DNA, which can activate oncogenesis or inhibit tumor suppression, were traditionally thought to be crucial factors for the initiation of carcinogenesis, recent studies have demonstrated that other molecular events such as transcription activation, signal transduction, oncogene amplification, and recombination, also constitute significant contributing factors [231, 232]. Studies have shown that mercury and other toxic metals effect cellular organelles and adversely affect their biologic functions [231, 233].…”

Section: Mercurymentioning

confidence: 99%

“…Although mutations of DNA, which can activate oncogenesis or inhibit tumor suppression, were traditionally thought to be crucial factors for the initiation of carcinogenesis, recent studies have demonstrated that other molecular events such as transcription activation, signal transduction, oncogene amplification, and recombination, also constitute significant contributing factors [231, 232]. Studies have shown that mercury and other toxic metals effect cellular organelles and adversely affect their biologic functions [231, 233]. Accumulating evidence also suggests that ROS play a major role in the mediation of metal-induced cellular responses and carcinogenesis [234–236].…”

Section: Mercurymentioning

confidence: 99%

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Heavy Metal Toxicity and the Environment

Tchounwou

Yedjou

Patlolla

et al. 2012

Experientia Supplementum

4,760

2,809

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Heavy metals are naturally occurring elements that have a high atomic weight and a density at least 5 times greater than that of water. Their multiple industrial, domestic, agricultural, medical and technological applications have led to their wide distribution in the environment; raising concerns over their potential effects on human health and the environment. Their toxicity depends on several factors including the dose, route of exposure, and chemical species, as well as the age, gender, genetics, and nutritional status of exposed individuals. Because of their high degree of toxicity, arsenic, cadmium, chromium, lead, and mercury rank among the priority metals that are of public health significance. These metallic elements are considered systemic toxicants that are known to induce multiple organ damage, even at lower levels of exposure. They are also classified as human carcinogens (known or probable) according to the U.S. Environmental Protection Agency, and the International Agency for Research on Cancer. This review provides an analysis of their environmental occurrence, production and use, potential for human exposure, and molecular mechanisms of toxicity, genotoxicity, and carcinogenicity.

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Section: Mercurymentioning

confidence: 99%

Section: Mercurymentioning

confidence: 99%

Heavy Metal Toxicity and the Environment

Tchounwou

Yedjou

Patlolla

et al. 2012

Experientia Supplementum

4,760

2,809

View full text Add to dashboard Cite

show abstract

“…84 According to studies conducted by Leaner et al and Zalups et al, Hg has negative effects on cellular organelles and their biological functions. 85,86 There is a controversy surrounding exposure to Hg and carcinogenesis. Some studies have indicated that Hg is genotoxic.…”

Section: à2mentioning

confidence: 99%

Cellular pathologies and genotoxic effects arising secondary to heavy metal exposure: A review

et al. 2019

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Environmental pollution is significant and oftentimes hazardous in the areas, where mining, foundries and smelters and other metallurgical operations are located. Systematic research on the chronic effects of metals started during the past century; nevertheless, it is evident that even today, there are large gaps in knowledge regarding the assessment of the health effects caused by environmental and occupational exposures to these metals. Heavy metals induce the production of reactive oxygen species (ROS) causing oxidative stress, make several repair-inhibiting cellular changes and alter the DNA repair processes. They favour the ‘false’ repairing of double-strand breaks (DSBs), propagate DNA mutations and induce carcinogenesis. A detailed literature search was performed using the MedLine/PubMed database. Depending on the mechanism of action, arsenicals can act as genotoxins, non-genotoxic agents and carcinogens. Cadmium can bind to proteins, reduce DNA repair, activate protein degradation, up-regulate cytokines and proto-oncogenes (c-fos, c-jun and c-myc), induce the expression of metallothionein, haeme-oxygenases, glutathione transferases, heat-shock proteins, acute-phase reactants and DNA polymerase β at lower concentrations. Inorganic mercury damages oxidative phosphorylation and electron transport pathways at the ubiquinone–cytochrome b5 locus and thus induces ROS production. Abandoned mining areas generate environmentally persistent waste. These specific sites urgently require maximally efficient and cheap remediation. This bears the need for methodologies employing green and sustainable remediation. Phytoremediation is important in that it is a prevalent in situ remediation technique. Its advantages include the use of solar energy, cost-effectiveness, easy operation, reduction in secondary contaminants, the use of biomass for biofuel production and low-cost adsorbents.

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“…Taken together, this suggests that AP-1 is a promising target for prevention and therapy in cancer and many other diseases [30].…”

Section: Introductionmentioning

confidence: 89%

The Extracts of Some Marine Invertebrates and Algae Collected off the Coast Waters of Vietnam Induce the Inhibitory Effects on the Activator Protein‐1 Transcriptional Activity in JB6 Cl41 Cells

Fedorov

Krasokhin

Shubina

et al. 2013

Journal of Chemistry

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It has previously been shown that inhibition of the transcriptional activity of the oncogenic nuclear factor AP-1 can result in cancer prevention. Marine invertebrates and alga are a rich source of natural compounds that possess various biological activities. The inhibitory effects of the extracts of Vietnamese marine organisms in relation to the AP-1 transcriptional activity were examined by the luciferase method using JB6 Cl41 cells stably expressing a luciferase reporter gene controlled by AP-1 DNA binding sequence. As was found, 71 species of marine sponges out of 148 species studied contain inhibitors of the AP-1 transcriptional activity. Therefore, marine organisms as a source of biologically active compounds have a great potential for isolation of the new cancer preventive compounds that inhibit the oncogenic AP-1 nuclear factor.

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Transcription Factors as Targets for Cancer Therapy: AP-1 a Potential Therapeutic Target

Cited by 14 publications

References 76 publications

Heavy Metal Toxicity and the Environment

Heavy Metal Toxicity and the Environment

Cellular pathologies and genotoxic effects arising secondary to heavy metal exposure: A review

The Extracts of Some Marine Invertebrates and Algae Collected off the Coast Waters of Vietnam Induce the Inhibitory Effects on the Activator Protein‐1 Transcriptional Activity in JB6 Cl41 Cells

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