Aromatase and 17β-hydroxysteroid dehydrogenase inhibition by flavonoids

Bail, J.C Le; Laroche, T; Marre-Fournier, Françoise; Habrioux, G

doi:10.1016/s0304-3835(98)00211-0

Cited by 126 publications

(83 citation statements)

References 15 publications

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“…Taken altogether, it seems that flavone skeleton may be prerequisite to elicit the activity. For example, chrysin was reported to interfere with steroid synthesis and metabolism [24,25]. The common observation with flavonoids, melanogenesis enhancing activity and cytotoxicity, may not be explained by a single defined action but involves multifunction.…”

Section: Resultsmentioning

confidence: 99%

Effects of Quercetin on Mushroom Tyrosinase and B16-F10 Melanoma Cells

2007

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Abstract:In searching for tyrosinase inhibitors from plants using L-3,4-dihydroxyphenylalanine (L-DOPA) as a substrate, quercetin was found to be partially oxidized to the corresponding o-quinone under catalysis by mushroom tyrosinase (EC 1.14.18.1). Simultaneously, L-DOPA was also oxidized to dopaquinone and both o-quinones were further oxidized, respectively. The remaining quercetin partially formed adducts with dopaquinone through a Michael type addition. In general, flavonols form adducts with dopaquinone as long as their 3-hydroxyl group is free. Quercetin enhanced melanin production per cell in cultured murine B16-F10 melanoma cells, but this effect may be due in part to melanocytotoxicity. The concentration leading to 50% viable cells lost was established as 20 µM and almost complete lethality was observed at 80 µM.

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Section: Resultsmentioning

confidence: 99%

Effects of Quercetin on Mushroom Tyrosinase and B16-F10 Melanoma Cells

2007

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“…This raises the interesting possibility that flavonoids may act as regulators of the activity of P-450 enzymes involved in other metabolic pathways. Numerous examples of inhibition of mammalian or insect P-450s by dietary flavonoids have been reported with impact on the metabolism of drugs (44), the activation of procarcinogens (45), or the biosynthesis of steroid hormones (46,47). In the case of plants, the binding of nonsubstrate flavonoids to P-450 enzymes could have an impact on specific physiological functions and result in a regulatory cross-talk between independent pathways.…”

Section: Discussionmentioning

confidence: 99%

Flavonoid 6-Hydroxylase from Soybean (Glycine maxL.), a Novel Plant P-450 Monooxygenase

Latunde-Dada¹,

Cabello‐Hurtado²,

Czittrich³

et al. 2001

Journal of Biological Chemistry

113

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Cytochrome P-450-dependent hydroxylases are typical enzymes for the modification of basic flavonoid skeletons. We show in this study that CYP71D9 cDNA, previously isolated from elicitor-induced soybean (Glycine max L.) cells, codes for a protein with a novel hydroxylase activity. When heterologously expressed in yeast, this protein bound various flavonoids with high affinity (1.6 to 52 M) and showed typical type I absorption spectra. These flavonoids were hydroxylated at position 6 of both resorcinol-and phloroglucinol-based A-rings. Flavonoid 6-hydroxylase (CYP71D9) catalyzed the conversion of flavanones more efficiently than flavones. Isoflavones were hardly hydroxylated. As soybean produces isoflavonoid constituents possessing 6,7-dihydroxy substitution patterns on ring A, the biosynthetic relationship of flavonoid 6-hydroxylase to isoflavonoid biosynthesis was investigated. Recombinant 2-hydroxyisoflavanone synthase (CYP93C1v2) efficiently used 6,7,4-trihydroxyflavanone as substrate. For its structural identification, the chemically labile reaction product was converted to 6,7,4-trihydroxyisoflavone by acid treatment. The structures of the final reaction products for both enzymes were confirmed by NMR and mass spectrometry. Our results strongly support the conclusion that, in soybean, the 6-hydroxylation of the A-ring occurs before the 1,2-aryl migration of the flavonoid B-ring during isoflavanone formation. This is the first identification of a flavonoid 6-hydroxylase cDNA from any plant species.Flavonoids are a diverse group of natural products that serve important roles in plants during growth, during development, and in defense against microorganisms and pests (1, 2). These compounds are synthesized from phenylpropanoid-and acetate-derived precursors through central pathways furnishing basic C 6 -C 3 -C 6 flavonoid skeletons and, in addition, through a variety of reactions leading to a range of modified aglycones and subsequently to their glycosylated derivatives within each flavonoid class. Many of the enzymes of flavonoid biosynthesis have been extensively studied (3), and recent molecular biological approaches have complemented biochemical methods in elucidating the mechanism and regulation of flavonoid biosynthesis (4). Typical enzymes belonging to the complex branch pathways for the elaboration of flavonoid skeletons are cytochrome P-450-dependent hydroxylases (3), such as flavonoid 3Ј-hydroxylase (5), flavonoid 3Ј,5Ј-hydroxylase (6), isoflavone 2Ј-hydroxylase (7), flavanone 2-hydroxylase (8), flavone synthase II (9, 10), and 2-hydroxyisoflavanone synthase (2HIS) 1 (11-13). Whereas flavonoid 3Ј-hydroxylase and flavonoid 3Ј,5Ј-hydroxylase are responsible for the formation of the 3Ј,5Ј-hydroxylation pattern of the flavonoid B-ring, hydroxylation of the isoflavone B-ring at the 2Ј position (isoflavone 2Ј-hydroxylase) is one of the key reactions leading to pterocarpan structures. The formation of flavones and isoflavones from flavanones is catalyzed by several evolutionarily related P-450s, either in a ...

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“…Studies by Le Bail et al (62) demonstrated that apigenin is an effective inhibitor of aromatose and 17ß-hydroxysteroid dehydrogenase activities in human placental microsomes, with resulting effects on steroid metabolism. Oral administration of apigenin was shown to cause a significant increase in uterine weight and overall uterine concentration of estrogen receptor (ER)-· in female mice (63).…”

Section: Achillea Millefoliummentioning

confidence: 99%

Apigenin and cancer chemoprevention: Progress, potential and promise (Review)

Patel

Shukla²,

Gupta³

2007

Int J Oncol

311

362

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Abstract. Cancer is one of the major public health burdens in the United States and in other developed countries, causing approximately 7 million deaths every year worldwide. Cancer rates vary dramatically in different regions and populations around the globe, especially between developing and developed nations. Changes in cancer prevalence patterns occur within regions as their populations age or become progressively urbanized. Migration has also contributed to such variations as changes in dietary habits influence cancer rates. These epidemiologic findings strongly suggest that cancer rates are influenced by environmental factors including diet, which is largely preventable. Approaches to prevent cancer include overlapping strategies viz. chemoprevention or dietary cancer prevention. Chemoprevention aims at prevention or reversal of the initiation phase of carcinogenesis or arrest at progression of carcinogenesis through the administration of naturally occurring constituents or pharmacological agents. Cancer prevention through diet may be largely achievable by increased consumption of fruits and vegetables. Considerable attention has been devoted to identifying plant-derived dietary agents which could be developed as promising chemopreventives. One such agent is apigenin. A naturally occurring plant flavone (4', 5, 7,-trihydroxyflavone) abundantly present in common fruits and vegetables including parsley, onions, oranges, tea, chamomile, wheat sprouts and some seasonings. Apigenin has been shown to possess remarkable anti-inflammatory, antioxidant and anti-carcinogenic properties. In the last few years, significant progress has been made in studying the biological effects of apigenin at cellular and molecular levels. This review examines the cancer chemopreventive effects of apigenin in an organ-specificity format, evaluating its limitations and its considerable potential for development as a cancer chemopreventive agent.

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Aromatase and 17β-hydroxysteroid dehydrogenase inhibition by flavonoids

Cited by 126 publications

References 15 publications

Effects of Quercetin on Mushroom Tyrosinase and B16-F10 Melanoma Cells

Effects of Quercetin on Mushroom Tyrosinase and B16-F10 Melanoma Cells

Flavonoid 6-Hydroxylase from Soybean (Glycine maxL.), a Novel Plant P-450 Monooxygenase

Apigenin and cancer chemoprevention: Progress, potential and promise (Review)

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