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Beyond DNA binding - a review of the potential mechanisms mediating quinacrine's therapeutic activities in parasitic infections, inflammation, and cancers.

Ehsanian R, Van Waes C, Feller SM - Cell Commun. Signal (2011)

Bottom Line: This is an in-depth review of the history of quinacrine as well as its pharmacokinetic properties and established record of safety as an FDA-approved drug.The potential uses of quinacrine as an anti-cancer agent are discussed with particular attention to its actions on nuclear proteins, the arachidonic acid pathway, and multi-drug resistance, as well as its actions on signaling proteins in the cytoplasm.In particular, quinacrine's role on the NF-κB, p53, and AKT pathways are summarized.

View Article: PubMed Central - HTML - PubMed

Affiliation: Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA. rezae@stanford.edu.

ABSTRACT
This is an in-depth review of the history of quinacrine as well as its pharmacokinetic properties and established record of safety as an FDA-approved drug. The potential uses of quinacrine as an anti-cancer agent are discussed with particular attention to its actions on nuclear proteins, the arachidonic acid pathway, and multi-drug resistance, as well as its actions on signaling proteins in the cytoplasm. In particular, quinacrine's role on the NF-κB, p53, and AKT pathways are summarized.

No MeSH data available.


Related in: MedlinePlus

The arachidonic acid pathway and its role in tumor promotion. (A) Potential inhibitory role of quinacrine in the arachidonic acid pathway. (B) Potential role of arachidonic acid pathway in tumor promotion. Adapted from http://en.wikipedia.org/wiki/File:Eicosanoid_synthesis.png; retrieved January 2010 and Ulrich [278].
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Figure 2: The arachidonic acid pathway and its role in tumor promotion. (A) Potential inhibitory role of quinacrine in the arachidonic acid pathway. (B) Potential role of arachidonic acid pathway in tumor promotion. Adapted from http://en.wikipedia.org/wiki/File:Eicosanoid_synthesis.png; retrieved January 2010 and Ulrich [278].

Mentions: Manipulations of the arachidonic acid pathway (Figure 2) have received considerable attention in the chemoprevention of cancer [176-180]. Agents which inhibit this pathway have been demonstrated to hold promise in the chemoprevention of prostate, gastrointestinal, lung as well as esophageal cancer [177,181-184]. Although cyclooxygenase has been the focus of many anti-neoplastic agents targeting the arachidonic acid pathway [185], other components of the pathway could potentially also be promising targets. One such putative target, PLA2, hydrolyzes the sn-2-acyl bond of membrane phospholipids to produce arachidonic acid (Figure 2), which has been implicated in a variety of signal transduction events, including those regulating malignant cell proliferation [186,187]. Histological studies suggest that membrane phospholipase A2 expression levels are associated with tumor aggressiveness in gastric [188] and breast cancers [189].


Beyond DNA binding - a review of the potential mechanisms mediating quinacrine's therapeutic activities in parasitic infections, inflammation, and cancers.

Ehsanian R, Van Waes C, Feller SM - Cell Commun. Signal (2011)

The arachidonic acid pathway and its role in tumor promotion. (A) Potential inhibitory role of quinacrine in the arachidonic acid pathway. (B) Potential role of arachidonic acid pathway in tumor promotion. Adapted from http://en.wikipedia.org/wiki/File:Eicosanoid_synthesis.png; retrieved January 2010 and Ulrich [278].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3117821&req=5

Figure 2: The arachidonic acid pathway and its role in tumor promotion. (A) Potential inhibitory role of quinacrine in the arachidonic acid pathway. (B) Potential role of arachidonic acid pathway in tumor promotion. Adapted from http://en.wikipedia.org/wiki/File:Eicosanoid_synthesis.png; retrieved January 2010 and Ulrich [278].
Mentions: Manipulations of the arachidonic acid pathway (Figure 2) have received considerable attention in the chemoprevention of cancer [176-180]. Agents which inhibit this pathway have been demonstrated to hold promise in the chemoprevention of prostate, gastrointestinal, lung as well as esophageal cancer [177,181-184]. Although cyclooxygenase has been the focus of many anti-neoplastic agents targeting the arachidonic acid pathway [185], other components of the pathway could potentially also be promising targets. One such putative target, PLA2, hydrolyzes the sn-2-acyl bond of membrane phospholipids to produce arachidonic acid (Figure 2), which has been implicated in a variety of signal transduction events, including those regulating malignant cell proliferation [186,187]. Histological studies suggest that membrane phospholipase A2 expression levels are associated with tumor aggressiveness in gastric [188] and breast cancers [189].

Bottom Line: This is an in-depth review of the history of quinacrine as well as its pharmacokinetic properties and established record of safety as an FDA-approved drug.The potential uses of quinacrine as an anti-cancer agent are discussed with particular attention to its actions on nuclear proteins, the arachidonic acid pathway, and multi-drug resistance, as well as its actions on signaling proteins in the cytoplasm.In particular, quinacrine's role on the NF-κB, p53, and AKT pathways are summarized.

View Article: PubMed Central - HTML - PubMed

Affiliation: Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA. rezae@stanford.edu.

ABSTRACT
This is an in-depth review of the history of quinacrine as well as its pharmacokinetic properties and established record of safety as an FDA-approved drug. The potential uses of quinacrine as an anti-cancer agent are discussed with particular attention to its actions on nuclear proteins, the arachidonic acid pathway, and multi-drug resistance, as well as its actions on signaling proteins in the cytoplasm. In particular, quinacrine's role on the NF-κB, p53, and AKT pathways are summarized.

No MeSH data available.


Related in: MedlinePlus