Relationship between flavonoid structure and inhibition of phosphatidylinositol 3-kinase: A comparison with tyrosine kinase and protein kinase C inhibition

Agullo, Georgine; Gamet-Payrastre, Laurence; Manenti, Stéphane; Viala, Cécile; Rémésy, Christian; Chap, Hugues; Payrastre, Bernard

doi:10.1016/s0006-2952(97)82453-7

Cited by 510 publications

(349 citation statements)

References 29 publications

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“…Quercetin has been shown to inhibit the enzymes involved in cell proliferation and in the cell signal transduction pathway including protein kinase C [5], tyrosine kinase [6], cdc25 phosphatase [7], PI-3 kinase [8], PAkt [9], DNA topoisomerase II [10], and c-Jun N-terminal kinase (JNK) [11]. Quercetin has a wide range of biological activities including inhibition of mutant p53 expression [12], and androgen receptor expression and function in LNCaP cells [13].…”

Section: Introductionmentioning

confidence: 99%

Quercetin augments TRAIL-induced apoptotic death: Involvement of the ERK signal transduction pathway

Kim

Lee

Jeong

et al. 2008

Biochemical Pharmacology

157

115

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Combined treatment with quercetin and TRAIL induced cytotoxicity and enhanced annexin V staining and poly (ADP-ribose) polymerase (PARP) cleavage in human prostate cancer cell lines DU-145 and PC-3. These indicators of apoptosis resulted from the activation of caspase-8, -9, and -3. Although the expression levels of FLIPs, cIAP1, cIAP2, and the Bcl-2 family were not changed in quercetin-treated cells, significant downregulation of survivin occurred. Knockdown survivin by siRNA significantly increased TRAIL-induced apoptosis. We hypothesized that quercetin-induced activation of MAPK (ERK, p38, JNK) is responsible for downregulation of survivin gene expression. To test this hypothesis, we selectively inhibited MAPK during treatment with quercetin. Our data demonstrated that inhibitor of ERK (PD98059), but not p38 MAPK (SB203580) or JNK (SP600125), significantly maintained the intracellular level of survivin during treatment with quercetin. Interestingly, PD98059 also prevented quercetin-induced deacetylation of histone H3. Data from survivin promoter activity assay suggest that the Sp1 transcription factor binds to the survivin promoter region and quercetin inhibits its binding activity through deacetylation of histone H3. Quercetin-induced activation of the ERK-MSK1 signal transduction pathway may be responsible for deacetylation of histone H3. Taken together, our findings suggest that quercetin enhances TRAIL induced apoptosis by inhibition of survivin expression, through ERK-MSK1-mediated deacetylation of H3.

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Section: Introductionmentioning

confidence: 99%

Quercetin augments TRAIL-induced apoptotic death: Involvement of the ERK signal transduction pathway

Kim

Lee

Jeong

et al. 2008

Biochemical Pharmacology

157

115

View full text Add to dashboard Cite

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“…The most abundant flavonol in the diet is quercetin, which possesses biological activities such as antioxidative (Chopra et al, 2000;Fuhrman & Aviram, 2001), anticarcinogenic (Pereira et al, 1996;Caltagirone et al, 1997) and enzyme-inhibiting activities (Siess et al, 1995;Agullo et al, 1997;Conseil et al, 1998). Other flavonoid subgroups of interest are for instance the flavanones.…”

Section: Introductionmentioning

confidence: 99%

Plasma concentrations of the flavonoids hesperetin, naringenin and quercetin in human subjects following their habitual diets, and diets high or low in fruit and vegetables

et al. 2002

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Objectives: To determine the fasting plasma concentrations of quercetin, hesperetin and naringenin in human subjects consuming their habitual diets, and diets either high or low in fruit and vegetables. To investigate whether plasma concentrations of flavanones can serve as biomarkers of their intake. Design: This was a cross-over, strictly controlled dietary intervention consisting of a 2 week baseline period, and two 5 week dietary periods with a 3 week wash-out period in between. The low-vegetable diet contained few fruit and vegetables and no citrus fruit. The high-vegetable diet provided various fruits and vegetables daily including on average one glass of orange juice, one-half orange and one-half mandarin. Subjects: Thirty-seven healthy females. Results: The high-vegetable diet provided 132 mg of hesperetin and 29 mg of naringenin. The low-vegetable diet contained no flavanones. The mean plasma hesperetin concentration increased from 12.2 nmol=l after the low-vegetable diet to 325 nmol=l after the high-vegetable diet. The respective increase for naringenin was from < 73.5 nmol=l for all subjects to a mean value of 112.9 nmol=l. The mean plasma quercetin concentration was 52 nmol=l after the baseline period, during which habitual diets were consumed, and it did not change significantly during the intervention. Interindividual variation in the plasma levels of hesperetin and naringenin was marked and, after the baseline and wash-out periods, and the low-vegetable diet, a majority of the samples had plasma flavanone levels below the limit of detection. After the high-vegetable diet, hesperetin and naringenin were detectable in 54 and 22% of all samples. Quercetin was detectable in nearly all samples after all study periods. Conclusion: Hesperetin, naringenin and quercetin are bioavailable from the diet, but the plasma concentrations of hesperetin and naringenin are poor biomarkers of intake.

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“…DRB and apigenin are marketed as "specific" CK2 inhibitors; the former however displays rather high IC 50 values (around 20 µM) and inhibits CK1 and possibly other protein kinases with comparable efficiency (15). Apigenin is more potent, but as in other general flavonoids, its specificity is quite broad (14,16). Emodin, among CK2 inhibitors, is of special interest as it is the active principle of Rheum palmatum, an herbal medicine widely used in Asia against several diseases, including leukemia (11).…”

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confidence: 99%

Inhibition of Protein Kinase CK2 by Condensed Polyphenolic Derivatives. An in Vitro and in Vivo Study

et al. 2004

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ATP site-directed inhibitors that can target individual kinases are powerful tools for use in signal transduction research, all the more so in the case of a pleiotropic, constitutively active protein kinase such as CK2, which is not turned on in response to specific stimuli. By screening a library of more than 200 derivatives of natural polyphenolic compounds, we have identified 16 molecules which inhibit CK2 with IC 50 values of e1 µM. They belong to the classes of anthraquinones (six compounds), xanthenones (two compounds), fluorenones (one compound), and coumarins (seven compounds), and their inhibitory potency correlates with the presence of nitro, amino, or halogen substituents at specific positions. Three of the most potent inhibitors, MNX (1,8-dihydroxy-4-nitroxanthen-9-one), NBC (8-hydroxy-4-methyl-9-nitrobenzo[g]chromen-2-one), and DBC (3,8-dibromo-7-hydroxy-4-methylchromen-2-one), whose IC 50 values range between 0.13 and 0.36 µM, are quite specific toward CK2 within a panel of 33 protein kinases tested. Treatment of Jurkat cells with these compounds promotes inhibition of endogenous CK2 and induction of apoptosis. A correlation is observed between their efficacy as CK2 inhibitors (as judged from IC 50 values) and their capacity to induce cell death (DC 50 values). Mutations of the unique CK2R residues Val66 and/or Ile174 to alanine have a detrimental effect on inhibition by these compounds with 16-67-fold increases in IC 50 values. The combined usage of these reagents can be exploited to gain information about cellular functions mediated by CK2.

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Relationship between flavonoid structure and inhibition of phosphatidylinositol 3-kinase: A comparison with tyrosine kinase and protein kinase C inhibition

Cited by 510 publications

References 29 publications

Quercetin augments TRAIL-induced apoptotic death: Involvement of the ERK signal transduction pathway

Quercetin augments TRAIL-induced apoptotic death: Involvement of the ERK signal transduction pathway

Plasma concentrations of the flavonoids hesperetin, naringenin and quercetin in human subjects following their habitual diets, and diets high or low in fruit and vegetables

Inhibition of Protein Kinase CK2 by Condensed Polyphenolic Derivatives. An in Vitro and in Vivo Study

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