Inhibition by green tea catechins of metabolic activation of procarcinogens by human cytochrome P450

Muto, Shuichi; Fujita, Ken‐ichi; Yamazaki, Yuko; Kamataki, Tetsuya

doi:10.1016/s0027-5107(01)00204-4

Cited by 181 publications

(111 citation statements)

References 39 publications

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“…Furthermore, the Ki value of EGCG for CYP1A2-mediated 7-ethoxyresorufin Odeethylation was 9.50 µM, in good agreement with our result, but the inhibition type was noncompetitive (25). …”

Section: Discussionsupporting

confidence: 91%

Inhibitory Effects of Eight Green Tea Catechins on Cytochrome P450 1A2, 2C9, 2D6, and 3A4 Activities

et al. 2016

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-PURPOSE:Green tea is a traditional beverage that has been enjoyed by the Japanese to this day. Recently, there has been an increase in the consumption of green tea beverage having high concentrations of catechins, such as (-)-epigallocatechin-3-O-gallate (EGCG). Many people tend to ingest large amounts of catechins through the frequent consumption of green tea beverage, and this dietary habit may lead to unwanted interactions between the catechins in green tea and medicinal drug. METHODS: The inhibitory effects of eight green tea catechins on drug metabolizing enzymes, cytochrome P450 (CYP) 1A2, 2C9, 2D6, and 3A4, were investigated in human liver microsomes. Incubation was initiated by the addition of cocktail probe drugs that served as specific substrates for each CYP, and the resulting metabolites were analyzed by LC-MS. RESULTS: From a comparison of the fifty percent inhibitory concentration (IC50) values of the eight green tea catechins, it was found that non-gallated catechins did not inhibit CYPs, whereas gallated catechins inhibited all CYPs except CYP2D6. Among them, CYP2C9 was most strongly inhibited by (-)-catechin-3-Ogallate (CG) (7.60 µM), and CYP1A2 was most strongly inhibited by EGCG (8.93 µM). Catechin gallate exhibited non-competitive inhibition of CYP2C9, and its Ki value was 9.76 ± 0.47µM. The present study is the first to report the inhibitory effect of CG on CYP2C9. In contrast, EGCG showed competitive inhibition of CYP1A2, and its Ki value was 14.3 ± 0.09 µM. CONCLUSION: Previous reports had predicted that plasma EGCG concentration reached 7.4 µM after ingesting green tea having high concentrations of catechins. That concentration of EGCG is equivalent to one-half to one-third of its Ki value for CYP1A2 and CYP3A4 in this study. The ingestion of beverages containing large amounts of green tea catechins together with drugs that are metabolized by CYP1A2, CYP2C9, and CYP3A4 should be avoided.

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“…Furthermore, the Ki value of EGCG for CYP1A2-mediated 7-ethoxyresorufin Odeethylation was 9.50 µM, in good agreement with our result, but the inhibition type was noncompetitive (25). …”

Section: Discussionsupporting

confidence: 91%

Inhibitory Effects of Eight Green Tea Catechins on Cytochrome P450 1A2, 2C9, 2D6, and 3A4 Activities

et al. 2016

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“…In rats, midazolam metabolism was increased by green tea extracts, suggesting in vivo induction of CYP3A4. Inhibition of P450 activity in human liver microsomes was found by coincubating green tea extracts with P450 substrates (Muto et al, 2001;Nishikawa et al, 2004). However, in healthy volunteers, treatment with green tea extracts did not alter CYP3A4 or CYP2D6 activity .…”

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confidence: 90%

Effects of Green Tea Compounds on Irinotecan Metabolism

et al. 2006

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ABSTRACT:The effects of green tea compounds on the metabolism of irinotecan have never been investigated. We aimed to study whether catechins [ (ECG), and 44% (EGC) of the hepatocyte preparations. Phenobarbital increased the formation of SN-38G in 100% of the same hepatocyte preparations. In Hep G2 cells, no increase in SN-38G formation was observed. With the exception of ECG in one liver, catechins did not increase UGT1A1 mRNA levels. NPC production was also significantly increased in 40% of the hepatocyte preparations for each catechin. However, the production of 6␤-hydroxytestosterone remained unaffected in other hepatocyte preparations. At pharmacologically relevant concentrations, catechins are unlikely to inhibit the formation of irinotecan inactive metabolites when administered concomitantly. The induction effect of catechins on UGT1A1 seems to be modest and highly variable. Catechins do not induce CYP3A4 activity. The effect of acute and prolonged use of green tea on the pharmacokinetics of irinotecan in patients remains to be evaluated.

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“…Ингибирование метаболической активации ГА, например, за счёт инактивации цитохромов Р450 приводит к снижению уровня мутагенных молекул и антиканцерогенному эффекту. Обнаружено, что таким образом действуют некоторые полифенолы, в частности, катехины чая [23,24]. Ресвератрол с различной эффективностью ингибирует активность цитохромов CYP1A2, CYP1A1 и CYP1B1, с чем связывают его защитное действие против гетероциклических аминов, а также против ароматических аминов, полициклических ароматических углеводородов (ПАУ), генотоксичных катехоловых метаболитов эстрогена [25][26][27].…”

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Mechanisms of plant polyphenols anti-cancer effects I. Blockade of carcinogenesis initiation

Spasov

2012

BIOMED KHIM

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Mechanisms of anti-cancer effects of polyphenols, found in fruits, vegetables, spices and representing parts of daily nutrition, have been considered. These compounds may be the basis for development of cancer preventive preparations. They can block carcinogenesis initiation by inactivation of exogenous or endogenous genotoxic molecules including reactive oxygen species. Another mechanism consists in inhibition of activity and synthesis of carcinogen-metabolizing enzymes. Plant polyphenols also induce expression of antioxidant and detoxification enzymes genes.

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Inhibition by green tea catechins of metabolic activation of procarcinogens by human cytochrome P450

Cited by 181 publications

References 39 publications

Inhibitory Effects of Eight Green Tea Catechins on Cytochrome P450 1A2, 2C9, 2D6, and 3A4 Activities

Inhibitory Effects of Eight Green Tea Catechins on Cytochrome P450 1A2, 2C9, 2D6, and 3A4 Activities

Effects of Green Tea Compounds on Irinotecan Metabolism

Mechanisms of plant polyphenols anti-cancer effects I. Blockade of carcinogenesis initiation

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