Melittin Suppresses HIF-1 alpha/VEGF Expression through Inhibition of ERK and mTOR/p70S6K Pathway in Human Cervical Carcinoma Cells

Title
Melittin Suppresses HIF-1 alpha/VEGF Expression through Inhibition of ERK and mTOR/p70S6K Pathway in Human Cervical Carcinoma Cells
Author(s)
장현욱신재문[신재문]정윤정[정윤정]조현지[조현지]박광규[박광규]정일경[정일경]이인규[이인규]곽종영[곽종영]김철호[김철호]문성관[문성관]김원재[김원재]최영현[최영현]장영채[장영채]
Keywords
HYPOXIA-INDUCIBLE FACTOR; GROWTH-FACTOR EXPRESSION; FACTOR 1-ALPHA; CANCER CELLS; SIGNALING PATHWAY; BREAST-CANCER; FACTOR-I; TUMOR; ANGIOGENESIS; ACTIVATION
Issue Date
201307
Publisher
PUBLIC LIBRARY SCIENCE
Citation
PLOS ONE, v.8, no.7
Abstract
Objective: Melittin (MEL), a major component of bee venom, has been associated with various diseases including arthritis, rheumatism and various cancers. In this study, the anti-angiogenic effects of MEL in CaSki cells that were responsive to the epidermal growth factor (EGF) were examined. Methodology/Principal Findings: MEL decreased the EGF-induced hypoxia-inducible factor-1 alpha (HIF-1 alpha) protein and significantly regulated angiogenesis and tumor progression. We found that inhibition of the HIF-1 alpha protein level is due to the shortened half-life by MEL. Mechanistically, MEL specifically inhibited the EGF-induced HIF-1 alpha expression by suppressing the phosphorylation of ERK, mTOR and p70S6K. It also blocked the EGF-induced DNA binding activity of HIF-1 alpha and the secretion of the vascular endothelial growth factor (VEGF). Furthermore, the chromatin immunoprecipitation (ChIP) assay revealed that MEL reduced the binding of HIF-1 alpha to the VEGF promoter HRE region. The anti-angiogenesis effects of MEL were confirmed through a matrigel plus assay. Conclusions: MEL specifically suppressed EGF-induced VEGF secretion and new blood vessel formation by inhibiting HIF-1 alpha. These results suggest that MEL may inhibit human cervical cancer progression and angiogenesis by inhibiting HIF-1 alpha and VEGF expression.
URI
http://hdl.handle.net/YU.REPOSITORY/29323http://dx.doi.org/10.1371/journal.pone.0069380
ISSN
1932-6203
Appears in Collections:
약학대학 > 약학부 > Articles
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE