Gene interactions and pathways from curated databases and text-mining
PloS one 2013, PMID: 23936001

Melittin suppresses HIF-1α/VEGF expression through inhibition of ERK and mTOR/p70S6K pathway in human cervical carcinoma cells.

Shin, Jae-Moon; Jeong, Yun-Jeong; Cho, Hyun-Ji; Park, Kwan-Kyu; Chung, Il-Kyung; Lee, In-Kyu; Kwak, Jong-Young; Chang, Hyeun-Wook; Kim, Cheorl-Ho; Moon, Sung-Kwon; Kim, Wun-Jae; Choi, Yung-Hyun; Chang, Young-Chae

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.

RESULTS

MEL decreased the EGF-induced hypoxia-inducible factor-1α (HIF-1α) protein and significantly regulated angiogenesis and tumor progression. We found that inhibition of the HIF-1α protein level is due to the shortened half-life by MEL. Mechanistically, MEL specifically inhibited the EGF-induced HIF-1α expression by suppressing the phosphorylation of ERK, mTOR and p70S6K. It also blocked the EGF-induced DNA binding activity of HIF-1α and the secretion of the vascular endothelial growth factor (VEGF). Furthermore, the chromatin immunoprecipitation (ChIP) assay revealed that MEL reduced the binding of HIF-1α 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-1α. These results suggest that MEL may inhibit human cervical cancer progression and angiogenesis by inhibiting HIF-1α and VEGF expression.

Diseases/Pathways annotated by Medline MESH: Neovascularization, Pathologic, Uterine Cervical Neoplasms
Document information provided by NCBI PubMed

Text Mining Data

HIF-1a ⊣ MEL: " Mechanistically, MEL specifically inhibited the EGF induced HIF-1a expression by suppressing the phosphorylation of ERK, mTOR and p70S6K "

ERK ⊣ MEL: " Mechanistically, MEL specifically inhibited the EGF induced HIF-1a expression by suppressing the phosphorylation of ERK , mTOR and p70S6K "

mTOR ⊣ MEL: " Mechanistically, MEL specifically inhibited the EGF induced HIF-1a expression by suppressing the phosphorylation of ERK, mTOR and p70S6K "

p70S6K ⊣ MEL: " Mechanistically, MEL specifically inhibited the EGF induced HIF-1a expression by suppressing the phosphorylation of ERK, mTOR and p70S6K "

HIF-1a → EGF: " Mechanistically, MEL specifically inhibited the EGF induced HIF-1a expression by suppressing the phosphorylation of ERK, mTOR and p70S6K "

HIF-1a → ERK: " Mechanistically, MEL specifically inhibited the EGF induced HIF-1a expression by suppressing the phosphorylation of ERK , mTOR and p70S6K "

HIF-1a → mTOR: " Mechanistically, MEL specifically inhibited the EGF induced HIF-1a expression by suppressing the phosphorylation of ERK, mTOR and p70S6K "

HIF-1a → p70S6K: " Mechanistically, MEL specifically inhibited the EGF induced HIF-1a expression by suppressing the phosphorylation of ERK, mTOR and p70S6K "

vascular endothelial growth factor → EGF: " It also blocked the EGF induced DNA binding activity of HIF-1a and the secretion of the vascular endothelial growth factor ( VEGF ) "

HIF-1a → EGF: " It also blocked the EGF induced DNA binding activity of HIF-1a and the secretion of the vascular endothelial growth factor ( VEGF ) "

HIF-1a ⊣ MEL: " Furthermore, the chromatin immunoprecipitation ( ChIP ) assay revealed that MEL reduced the binding of HIF-1a to the VEGF promoter HRE region "

VEGF ⊣ MEL: " MEL specifically suppressed EGF induced VEGF secretion and new blood vessel formation by inhibiting HIF-1a "

VEGF → EGF: " MEL specifically suppressed EGF induced VEGF secretion and new blood vessel formation by inhibiting HIF-1a "

VEGF ⊣ MEL: " These results suggest that MEL may inhibit human cervical cancer progression and angiogenesis by inhibiting HIF-1a and VEGF expression "

HIF-1a ⊣ MEL: " These results suggest that MEL may inhibit human cervical cancer progression and angiogenesis by inhibiting HIF-1a and VEGF expression "

Manually curated Databases

No curated data.