Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Inhibitory Potential of Thelephoric Acid on CYP2J2 Activities in Human Liver Microsomes

Thelephoric acid의 CYP2J2 효소 활성 저해제 평가

  • Wu, Zhexue (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University) ;
  • Lee, Boram (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University) ;
  • Song, Kyung-Sik (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University) ;
  • Liu, Kwang-Hyeon (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University)
  • 오철학 (경북대학교 약학대학 약학과) ;
  • 이보람 (경북대학교 약학대학 약학과) ;
  • 송경식 (경북대학교 약학대학 약학과) ;
  • 류광현 (경북대학교 약학대학 약학과)
  • Received : 2013.09.12
  • Accepted : 2013.09.25
  • Published : 2013.09.30
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Abstract

Cytochrome P450 2J2 (CYP2J2) is an enzyme mainly found in human extrahepatic tissues, with predominant expression in the cardiovascular system. CYP2J2 plays important roles in the metabolism of endogenous metabolites and therapeutic drugs, such as arachidonic acid, astemizole, ebastine, and terfenadine. CYP2J2 is also overexpressed in human cancer tissues and cancer cell lines and may represent a potential target for therapy of human cancers. In this study, 10 natural products obtained from plants and microorganisms were screened as potential CYP2J2 inhibitors. Among them, thelephoric acid showed strong inhibition of astemizole O-demethylation activity ($IC_{50}=3.23{\mu}M$) in a dose-dependent manner. Evaluation of the substrate dependency of the inhibitory activity of thelephoric acid showed that it strongly inhibited CYP2J2-mediated ebastine hydroxylation ($IC_{50}=5.32{\mu}M$) and terfenadine hydroxylation ($IC_{50}=3.27{\mu}M$) in a substrate nondependent manner. The present data suggest that this compound might be a potential candidate for further evaluation for anticancer activity.

CYP2J2 효소는 간외의 조직에 존재 하는 효소로써, 주로 심혈관계에 발현되어 있다. CYP2J2는 내인성 대사체 및 여러 치료 약물들의 대사에 중요한 작용을 하고 있다. 또한 CYP2J2는 인체의 종양조직이나 종양 세포주에서 과발현되어 있어, 종양 치료를 위한 새로운 표적이 되고 있다. 본 연구에서는 천연물 10종을 대상으로 시토크롬 2J2 동효소에 저해능을 가지는 화합물을 발굴하고자 하였다. 10종의 천연물 중 thelephoric acid는 CYP2J2에 의해 매개되는 에바스틴($IC_{50}=5.32{\mu}M$), 아스테미졸($IC_{50}3.23{\mu}M$) 및 터페나딘($IC_{50}=3.27{\mu}M$) 대사를 강력하게 저해하였다. 향후, 이 약물을 대상으로 한 항암 활성 평가가 필요할 것으로 판단된다.

Keywords

References

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