Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Quercetin and related flavonoids are naturally occurring polyphenolic compounds with multiple pharmacological activities. Using cultured human umbilical vein endothelial cells, we investigated the effects of quercetin on endothelin (ET-1) and tissue plasminogen activator (t-PA) release induced by thrombin. We observed that when endothelial cells pretreated with 5 or 50 microM of quercetin were incubated for 4 and 24 h with thrombin, ET-1 concentration-dependently decreased (n = 6, P < 0.01, at 4 h IC50 = 1.54 microM, at 24 h IC50 = 2.78 microM). Under the same experimental conditions, quercetin significantly increased t-PA (n = 6, P < 0.01, at 4 h EC50 = 0.71 microM and at 24 hrs EC50 = 0.74 microM). In the same preparation, we evaluated prostacyclin (PGI2) release, induced by thrombin activated platelets, as determined by a 6-Keto-PGF1alpha radioimmunoassay. Following the treatment of cultured endothelial cells with activated platelets, the concentration of 6-Keto-PGF1alpha was significantly increased (P < 0.01). Quercetin (1, 5, and 20 microM) inhibited PGI2, in a concentration-dependent manner (n = 6, P < 0.05). Our data indicate that quercetin modulates the release of ET-1, t-PA, and PGI2 from vascular endothelial cells.
 ...
PMID:Effects of quercetin on the release of endothelin, prostacyclin and tissue plasminogen activator from human endothelial cells in culture. 1061 62

The induction of Hsp68 by heat shock (HS) and oxidative stress (OS) involves different pathways in C6 rat glioma cells. The pathways were analyzed by specific inhibitors of signal transduction cascades. Quercetin (inhibitor of PLA(2) and lipoxygenase) inhibited only the OS-induced but not the HS-induced expression of Hsp68. Preincubation with quinacrine (inhibitor of PLA(2)) before stress also suppressed the expression of Hsp68 only after oxidative stress. Moreover, another inhibitor of lipoxygenase (alpha-tocopherol) exclusively suppressed OS-induced Hsp68 expression. This different regulation was confirmed by exposing the cells to arachidonic acid (AA) during stress which strongly increased the induction of Hsp68 only after OS. PGE(2) (metabolite of cyclooxygenase) and indomethacin (inhibitor of cyclooxygenase) had no influence on Hsp68 expression in response to both stressors. The results suggest that the induction of Hsp68 by oxidative stress is mainly transmitted by the lipoxygenase pathway in C6 rat glioma cells.
 ...
PMID:Induction of Hsp68 by oxidative stress involves the lipoxygenase pathway in C6 rat glioma cells. 1079 93

Administration of quercetin, a common polyphenolic component of many vascular and edible plants including vegetables, fruits and tea significantly reduced the tumor volume in rats induced for mammary carcinoma using dimethyl benz (a) anthracene (DMBA). Dose response was assessed, by treating the animals with different doses (15-45 mg/kgbw) of quercetin and 25 mg/kgbw was taken as effective dose. Quercetin was administered as an intra tumoral injection once a week for 4 weeks. Serum levels of carcino embryonic antigen (CEA), a potent marker for tumor growth and invasion was significantly decreased on quercetin treatment. Quercetin caused a significant decrease in the activities of acid phosphatase and Cathepsin D in serum of experimental animals. Activities of lysosomal enzymes- (beta-D galactosidase, beta-D glucuronidase, beta-D glucosidase and sialidase), in serum and tissue were significantly altered in DMBA animals compared to control animals. However, quercetin treatment caused no significant change in lysosomal enzyme activities in tissues, whereas the activities were significantly lowered in serum. Partial purification of tissue type plasminogen activator (t-PA) from the tumor and kidney showed increased activity in the DMBA induced animals. Serum urokinase, -like plasminogen activator (u-PA) was also increased in animals with tumor, indicating tumor invasion. Administration of quercetin caused a significant decrease of both t-PA and u-PA. In conclusion, the present study suggests the possible role of quercetin in primary and invasive mammary tumor treatment. The above observations in vivo warrant further studies, due to the easy availability, common occurrence and low toxicity of this dietary bioflavonoid.
 ...
PMID:Suppression of tumor growth and invasion in 9,10 dimethyl benz(a) anthracene induced mammary carcinoma by the plant bioflavonoid quercetin. 1684 95

Polymer nanoparticles have emerged as a promising new strategy for the efficient delivery of drugs. They have several advantages when used as drug carriers, such as high stability, high capacity, improvement of drug bioavailability, as well as allowing for sustained drug release. Quercetin has therapeutic potential as an anticancer drug, but has poor solubility and low bioavailability. In this study it is shown that co-encapsulation of quercetin and fluorescent Silicon quantum dots (SiQDs) in poly (ethylene glycol)-block-polylactide (PEG-PLA) nanoparticles can be used for simultaneous in vitro imaging and to improve the biocompatibility of quercetin. Fluorescent imaging with SiQDs can provide a new concept to monitor the delivery of anti-cancer drugs. The nanoparticles are synthesized based on the double emulsion method and are extensively characterized and assayed for cytotoxicity in vitro. HepG2 cells are incubated with quercetin and SiQDs dual-loaded PEG-PLA nanoparticles, resulting in a red fluorescent staining which can be detected with a confocal microscope. PEG-PLA nanoparticle encapsulated quercetin suppresses human hepatoma HepG2 cell proliferation more effectively than the free-standing form. In addition, nanoparticle-encapsulated quercetin significantly inhibits hydrogen peroxide-induced DNA damage in HepG2 cells. These data show that nanocapsulated quercetin possesses the potential bioactivity to reduce the drug dosage frequency, as well as increase patient compliance. The combination of polymeric nanoparticles and semiconductor quantum dots can allow monitoring of delivery, improve aqueous solubility, and enhance biocompatibility. Such nanoparticulated systems could shape the future of drug delivery.
 ...
PMID:Co-encapsulation of biodegradable nanoparticles with silicon quantum dots and quercetin for monitored delivery. 2318 34

The spread of metastatic cancer cell is the main cause of death worldwide. Cellular and molecular basis of the action of phytochemicals in the modulation of metastatic cancer highlights the importance of fruits and vegetables. Quercetin is a natural bioflavonoid present in fruits, vegetables, seeds, berries, and tea. The cancer-preventive activity of quercetin is well documented due to its anti-inflammatory, anti-proliferative and anti-angiogenic activities. However, poor water solubility and delivery, chemical instability, short half-life, and low-bioavailability of quercetin limit its clinical application in cancer chemoprevention. A better understanding of the molecular mechanism of controlled and regulated drug delivery is essential for the development of novel and effective therapies. To overcome the limitations of accessibility by quercetin, it can be delivered as nanoconjugated quercetin. Nanoconjugated quercetin has attracted much attention due to its controlled drug release, long retention in tumor, enhanced anticancer potential, and promising clinical application. The pharmacological effect of quercetin conjugated nanoparticles typically depends on drug carriers used such as liposomes, silver nanoparticles, silica nanoparticles, PLGA (Poly lactic-co-glycolic acid), PLA (poly(D,L-lactic acid)) nanoparticles, polymeric micelles, chitosan nanoparticles, etc. In this review, we described various delivery systems of nanoconjugated quercetin like liposomes, silver nanoparticles, PLGA (Poly lactic-co-glycolic acid), and polymeric micelles including DOX conjugated micelles, metal conjugated micelles, nucleic acid conjugated micelles, and antibody-conjugated micelles on in vitro and in vivo tumor models; as well as validated their potential as promising onco-therapeutic agents in light of recent updates.
 ...
PMID:Quercetin Loaded Nanoparticles in Targeting Cancer: Recent Development. 3128 73