1,2,3,4,6-Penta-O-galloly-beta-D-glucose Suppresses Hypoxia-Induced Accumulation of Hypoxia-Inducible Factor-1α and Signaling in LNCaP Prostate Cancer Cells

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概要

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• Hypoxia is the hallmark of solid tumors and contributes to tumor angiogenesis mainly through activation of the transcription factor hypoxia-inducible factor-1 (HIF-1). In addition to upregulating vascular endothelial growth factor (VEGF) in angiogenesis, HIF-1 plays critical roles in the metabolism, proliferation, metastasis, and differentiation of cancer cells. We and others have previously shown that 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG) from Oriental herbal medicine possesses anti-angiogenic, anti-tumorigenic, and anti-diabetic activities. In the present study, we report that PGG inhibits hypoxia-induced protein accumulation, transcriptional activation, and mRNA expression of HIF-1α in LNCaP prostate cancer cells. PGG reduced cellular and secreted VEGF levels as well as mRNA expression in LNCaP cells. PGG suppressed capillary tube formation in human umbilical vein endothelial cells (HUVECs) maintained in conditioned medium of hypoxia-induced LNCaP cells, indicating that PGG has anti-angiogenic activity under hypoxic condition. Furthermore, PGG reduced expression of phosphoinositide 3-kinase (PI3K) as well as phosphorylation of AKT and mammalian target of rapamycin (mTOR), but not extracellular signal-regulated kinase (ERK) in LNCaP cells under hypoxic condition. Consistently, LY294002, a specific PI3K inhibitor, enhanced the inactivation of HIF-1α and AKT by PGG in LNCaP cells. Taken together, our results demonstrate that PGG inhibits hypoxia-mediated accumulation of HIF-1α as well as its downstream signaling to VEGF and PI3K/AKT/mTOR pathway in LNCaP prostate cancer cells.

著者

• KIM Sung-Hoon

  College of Oriental Medicine, Kyunghee University

• Jeong Soo-Jin

  College of Oriental Medicine, Kyung Hee University

• Lee Hyo-Jung

  College of Oriental Medicine, Kyung Hee University

• Lee Hyo-Jeong

  College of Oriental Medicine, Kyung Hee University

• Lee Hong-beom

  Division Of Ocean Science Korea Maritime University

• Lee Hyo-jung

  Coll. Of Oriental Medicine Kyung Hee Univ.

• Park Ki-Young

  College of Oriental Medicine, Kyung Hee University

• Kim Hyun-Seok

  The Hormel Institute, University of Minnesota

• Kim Sun-Hyung

  College of Oriental Medicine, Kyung Hee University

• Lim Sabina

  College of Oriental Medicine, Kyung Hee University

• Kim Ho-Cheol

  College of Oriental Medicine, Kyung Hee University

• Lü Junxuan

  College of Oriental Medicine, Kyung Hee University

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