Korean Journal of Food Science and Technology (한국식품과학회지)

Korean Society of Food Science and Technology (한국식품과학회)
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Delphinidin Suppresses Angiogenesis via the Inhibition of HIF-1α and STAT3 Expressions in PC3M Cells

전립선 암세포에서 delphinidin에 의한 HIF-1α와 STAT3 억제를 통한 혈관내피 성장 인자 발현 저해 효과

  • Kim, Mun-Hyeon (Research Institute of Biomedical Engineering, Catholic University of Daegu School of Medicine) ;
  • Kim, Mi-Hyun (Department of Physical Therapy, Inje University) ;
  • Park, Young-Ja (Department of Clinical Pathology, Sorabol College) ;
  • Chang, Young-Chae (Research Institute of Biomedical Engineering, Catholic University of Daegu School of Medicine) ;
  • Park, Yoon-Yub (Research Institute of Biomedical Engineering, Catholic University of Daegu School of Medicine) ;
  • Song, Hyun-Ouk (Research Institute of Biomedical Engineering, Catholic University of Daegu School of Medicine)
  • 김문현 (대구가톨릭대학교 의용생체공학연구소) ;
  • 김미현 (인제대학교 물리치료학과) ;
  • 박영자 (서라벌대학교 임상병리과) ;
  • 장영채 (대구가톨릭대학교 의용생체공학연구소) ;
  • 박윤엽 (대구가톨릭대학교 의용생체공학연구소) ;
  • 송현욱 (대구가톨릭대학교 의용생체공학연구소)
  • Received : 2015.10.01
  • Accepted : 2015.12.25
  • Published : 2016.02.29
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Abstract

Delphinidin is a blue-red pigment and one of the major anthocyanins in plants. It plays an important role in anti-oxidant, anti-inflammatory, anti-mutagenic and anti-cancer properties. In this study, we investigated the inhibitory effects of delphinidin on vascular endothelial growth factor (VEGF) gene expression, an important factor involved in angiogenesis and tumor progression in human prostate cancer. Delphinidin decreased levels of epidermal growth factor (EGF)-induced VEGF mRNA expression in PC-3M cells. The expression of the EGF-induced hypoxia inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) and signaling transducer and activator of transcription 3 (STAT3) proteins, which are the major transcription factors for VEGF, were inhibited by delphinidin. In addition, delphinidin decreases HRE-promoter reporter gene activity, suggesting that delphinidin can suppress the transcription of HIF-$1{\alpha}$ under EGF induction, leading to a decrease in the expression of VEGF. Delphinidin specifically suppressed the phosphorylation of Akt, p70S6K, and 4EBP1, but not the phosphorylation of EGFR. Therefore, our results suggest that delphinidin may inhibit human prostate cancer progression and angiogenesis by inhibiting HIF-$1{\alpha}$, STAT3 and VEGF gene expression.

델피니딘은 양전하를 뛰는 diphenylpropane의 polyphenolic ring 구조를 가진 주요한 안토시아닌 색소 중에 하나이다. 최근 연구에서 델피니딘은 항산화, 항염증 뿐만 아니라 항암 효능을 가진다고 보고되었다. 본 연구에서는 전립샘 암에서 종양의 성장과 신생혈관생성에 관련된 중요한 인자인 VEGF 발현에 대한 델피니딘의 억제 효과를 조사하였다. RT-PCR을 통해 델피니딘을 처리한 PC3M 전립샘 암세포 세포에서 EGF로 유도한 VEGF mRNA 발현 수준이 감소됨을 확인하였다. 또한 델피니딘은 VEGF의 전사인자인 HIF-$1{\alpha}$와 STAT3가 세포 핵으로 전위되는 것을 효과적으로 억제하였다. 한편 luciferase assay을 통해 HRE-promoter 활성을 확인해 본 결과, 델피니딘이 HIF-$1{\alpha}$의 전사 활성을 억제시켜 VEGF 발현을 감소시키는 것을 알 수 있었다. 그리고 델피니딘은 EGFR의 발현에는 영향을 미치지 않고, Akt, p70S6K, 4EBP1의 인산화를 특이적으로 억제하는 것으로 나타났다. 결론적으로 델피니딘이 HIF-$1{\alpha}$와 STAT3, VEGF 발현을 억제를 통하여 암세포 증식억제와 신생혈관형성을 억제하는 역할을 새롭게 확인하였다.

Keywords

References

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