Bioflavonoid interaction with rat uterine type ii binding sites and cell growth inhibition

Markaverich, Barry M.; Roberts, Rebecca; Alejandro, Mary A.; Johnson, Gregory A.; Middleditch, Brian S.; Clark, James H.

doi:10.1016/0022-4731(88)90078-7

Cited by 192 publications

(118 citation statements)

References 26 publications

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“…16 In contrast to the effects of quercetin and OR486, the inhibitory effects of estradiol were not blocked by luteolin ( Figure 2B and 2C).…”

Section: Barchiesi Et Al Er-independent Antimitogenesis By Estradiol mentioning

confidence: 81%

“…The hypothesis that the inhibitory effects of estradiol are caused by its conversion to methoxyestradiols is further supported by our observation that human VSMCs metabolize 2-hydroxyestradiol to 2-methoxyestradiol and that this metabolic step is blocked by quercetin and OR486. 12 Quercetin not only blocks the conversion of catecholestrogens to methoxyestrogens 12 but also binds to the type II ER, 16 which has been implicated in regulating cell growth. 16 The finding that in contrast to the effects of quercetin, the inhibitory effects of estradiol are not blocked by luteolin, a high-affinity type II ER ligand, 16 rules out the participation of type II ER and supports the conclusion that quercetin blocks the inhibitory effects of estradiol by inhibiting COMT and blocking the formation of methoxyestradiols.…”

Section: Discussionmentioning

confidence: 99%

“…12 Quercetin not only blocks the conversion of catecholestrogens to methoxyestrogens 12 but also binds to the type II ER, 16 which has been implicated in regulating cell growth. 16 The finding that in contrast to the effects of quercetin, the inhibitory effects of estradiol are not blocked by luteolin, a high-affinity type II ER ligand, 16 rules out the participation of type II ER and supports the conclusion that quercetin blocks the inhibitory effects of estradiol by inhibiting COMT and blocking the formation of methoxyestradiols. This contention is directly supported by the observations that OR486, an established COMT inhibitor, 18 blocked the metabolic conversion of 2-hydroxyestradiol to 2-methoxyestradiol by SMCs, as well as the antimitogenic effects of both estradiol and 2-hydroxyestradiol, but not of 2-methoxyestradiol.…”

Section: Discussionmentioning

confidence: 99%

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Methoxyestradiols Mediate Estradiol-Induced Antimitogenesis in Human Aortic SMCs

Barchiesi

Jackson²,

Gillespie³

et al. 2002

Hypertension

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Abstract-Estrogen receptors (ERs) are considered to mediate the ability of 17␤-estradiol (estradiol) to reduce injury-induced proliferation of vascular smooth muscle cells (VSMCs), leading to vascular lesions. However, the finding that estradiol attenuates formation of vascular lesions in response to vascular injury in knockout mice that lack either ER-␣ or ER-␤ challenges this concept. Our hypothesis is that the local metabolism of estradiol to methoxyestradiols, metabolites of estradiol with little affinity for ERs, mediates the ER-independent antimitogenic effects of estradiol on VSMCs. In human VSMCs, 2-methoxyestradiol and 2-hydroxyestradiol were more potent than was estradiol in inhibiting DNA synthesis ( 3 [H]-thymidine incorporation), collagen synthesis ( 3 [H]-proline incorporation), cell proliferation (cell number), and cell migration (movement of cells across a polycarbonate membrane). The inhibitory effects of estradiol on VSMCs were enhanced by cytochrome-P450 (CYP450) inducers 3-methylcholanthrene and phenobarbital. Moreover, the inhibitory effects of estradiol were blocked in the presence of the CYP450 inhibitor 1-aminobenzotriazole and the catechol-O-methyltransferase inhibitors quercetin and OR486. Both OR486 and quercetin blocked the conversion of 2-hydroxyestradiol to 2-methoxyestradiol; moreover, they blocked the antimitogenic effects of 2-hydroxyestradiol but not of 2-methoxyestradiol. The ER antagonist ICI182780 blocked the inhibitor effects of estradiol on VSMCs, but only at concentrations (Ͼ50 mol/L) that also inhibit the metabolism of estradiol to hydroxyestradiols (precursors of methoxyestradiols). In conclusion, the inhibitory effects of locally applied estradiol on human VSMCs are mediated via a novel ER-independent mechanism involving estradiol metabolism. These findings imply that vascular estradiol metabolism may be an important determinant of the cardiovascular protective effects of estradiol and that nonfeminizing estradiol metabolites may confer cardiovascular protection regardless of gender.

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“…16 In contrast to the effects of quercetin and OR486, the inhibitory effects of estradiol were not blocked by luteolin ( Figure 2B and 2C).…”

Section: Barchiesi Et Al Er-independent Antimitogenesis By Estradiol mentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Methoxyestradiols Mediate Estradiol-Induced Antimitogenesis in Human Aortic SMCs

Barchiesi

Jackson²,

Gillespie³

et al. 2002

Hypertension

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“…Many of these effects are apparently mediated via the interaction of phyto-oestrogens with mammalian oestrogen receptors. For example lignans and isoflavonoids compete with endogenous oestrogens for type I1 oestrogen binding sites and may thereby regulate the growth of oestrogen dependent tissues (Markaverich et al 1988). A second important effect of these compounds is the stimulation of endogenous production of sex hormone binding globulin (SHBG) which modulates the biological activity of oestrogen in humans.…”

Section: Oestrogen Metabolismmentioning

confidence: 99%

Anticarcinogenic Factors in Plant Foods: A New Class of Nutrients?

1994

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“…It has a high binding affinity (dissociation constant = 4-5 nM) for type II EBS and inhibits the oestradiol-stimulated growth of rat uterus and MCF-7 human breast cancer cells (Markaverich et al, 1988a(Markaverich et al, , 1990. MeHPLA is hydrolysed by MeHPLA esterase (MeHPLAase) to the free p-hydroxyphenyllactic acid (HPLA), which has a much lower binding affinity for type II EBS and is inactive in terms of cell growth inhibition (Markaverich et al, 1988b(Markaverich et al, , 1990. The activity of the MeHPLAase in rat uterus is stimulated by oestrogens in vivo (Markaverich et al, 1989).…”

mentioning

confidence: 99%

Prognostic significance of methyl-p-hydroxy-phenyllactate-esterase activity in laryngeal squamous cell carcinoma

et al. 1998

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Summary We assayed methyl-p-hydroxyphenyllactate esterase (MeHPLAase) activity in 63 cases of primary laryngeal squamous cell carcinoma. MeHPLAase activity did not show any correlation with oestrogen, progesterone and epidermal growth factor (EGF) receptor levels. No significant relationship was found between MeHPLAase activity and age, sex, tumour site, T classification, stage of disease and EGFR status, whereas a significant inverse relationship was found between enzymatic activity and neck lymph node positivity at presentation. The median value of MeHPLAase activity tended to be higher in tumours with low histopathological grade than in those with high histopathological grade. Dunng the follow-up period (median 50 months, range 2-90 months) locoregional recurrences were observed in 31 out of 63 (49%) cases. At the end of the study, 27 out of 63 (43%) patients had died of cancer. Cox univarate analysis using MeHPLAase activity as a continuous covariate showed that the levels of enzymatic activity were inversely associated with the risk of death and relapse. Assuming the mean value of enzymatic activity as the cut-off value, we found a statistically significant relationship between high MeHPLAase activity and longer relapse-free and overall survival. MeHPLAase activity status retained its prognostic significance also in the lymph node-negative subgroup of patients. On multivariate analysis, both EGFR and MeHPLAase activity proved to be independent factors for predicting a short relapse and the overall survival.

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Bioflavonoid interaction with rat uterine type ii binding sites and cell growth inhibition

Cited by 192 publications

References 26 publications

Methoxyestradiols Mediate Estradiol-Induced Antimitogenesis in Human Aortic SMCs

Methoxyestradiols Mediate Estradiol-Induced Antimitogenesis in Human Aortic SMCs

Anticarcinogenic Factors in Plant Foods: A New Class of Nutrients?

Prognostic significance of methyl-p-hydroxy-phenyllactate-esterase activity in laryngeal squamous cell carcinoma

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