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Comparative α-Naphthoflavone and β-Naphthoflavone Inhibits the Formation of a Carcinogenic Estrogen Metabolite

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Abstract

17β-Estradiol (E2) is hydrolyzed to 2-hydroxy-E2 and 4-hydroxy-E2 (4-OH-E2) via cytochrome P450 (CYP) 1B1. In estrogen target tissues including the mammary gland, ovaries and uterus, CYP1B1 is highly expressed, and 4-OH-E2 is predominantly formed in cancerous tissues. In the present study, we investigated the inhibitory activity of α-naphthoflavone and β-naphthoflavone against CYP1B1 using estrogen E2 as substrate in vitro to reveal structure–activity relationship between structure of flavonoids and inhibition. The results showed that α-naphthoflavone and β-naphthoflavone possessed inhibitory activity against CYP1B1-mediated E2 and the inhibition of α-naphthoflavone was stronger than β-naphthoflavone. By kinetic analyses, α-naphthoflavone displayed uncompetitive inhibition, while β-naphthoflavone displayed mixed inhibition. Taken together, the data suggested that the benzo at A ring of flavonoids play a prominent role in CYP1B1 inhibition, especially 7,8-benzo is better than 5,6-benzo. This study may help to reveal the relationship between the structure of flavonoids and the inhibition CYP1B1 for discovering new drugs in cancer therapy and prevention.

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Abbreviations

E2:

17β-Estradiol

2-OH-E2:

2-Hydroxy-17β-estradiol

4-OH-E2:

4-Hydroxy-17β-estradiol

CYP1B1:

Cytochrome P450 (CYP) 1B1

Δ 6-E1:

Δ 6-Estrone

IC50:

50 % Inhibition

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Acknowledgments

This work was supported partly by the Science Foundation of Heilongjiang University of Chinese Medicine (No. 201208).

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Authors and Affiliations

  1. School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, 150040, People’s Republic of China

    Xin Meng, Zhigang Wang, Lianrong Yang, Shujun Xu, Yuan Tian & Hui Sun

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  1. Xin Meng
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  2. Zhigang Wang
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  3. Lianrong Yang
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  4. Shujun Xu
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  5. Yuan Tian
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  6. Hui Sun
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Correspondence to Xin Meng.

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Meng, X., Wang, Z., Yang, L. et al. Comparative α-Naphthoflavone and β-Naphthoflavone Inhibits the Formation of a Carcinogenic Estrogen Metabolite. Int J Pept Res Ther 23, 291–295 (2017). https://doi.org/10.1007/s10989-016-9560-6

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