Melittin restores PTEN expression by down-regulating HDAC2 in human hepatocelluar carcinoma HepG2 cells.
Melittin is a water-soluble toxic peptide derived from the venom of the bee. Although many studies show the anti-tumor activity of melittin in human cancer including glioma cells, the underlying mechanisms remain elusive. Here the effect of melittin on human hepatocelluar carcinoma HepG2 cell proliferation in vitro and further mechanisms was investigated. We found melittin could inhibit cell proliferation in vitro using Flow cytometry and MTT method. Besides, we discovered that melittin significantly downregulated the expressions of CyclinD1 and CDK4. Results of western Blot and Real-time PCR analysis indicated that melittin was capable to upregulate the expression of PTEN and attenuate histone deacetylase 2 (HDAC2) expression. Further studies demonstrated that knockdown of HDAC2 completely mimicked the effects of melittin on PTEN gene expression. Conversely, it was that the potential utility of melittin on PTEN expression was reversed in cells treated with a recombinant pEGFP-C2-HDAC2 plasmid. In addition, treatment with melittin caused a downregulation of Akt phosphorylation, while overexpression of HDAC2 promoted Akt phosphorylation. These findings suggested that the inhibitory of cell growth by melittin might be led by HDAC2-mediated PTEN upregulation, Akt inactivation, and inhibition of the PI3K/Akt signaling pathways.
School of pharmacy, Anhui key laboratory of bioactivity of natural products, Anhui Medical University, Hefei, Anhui Province, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei, Anhui Province, China.
Hui
H
Zhang
School of pharmacy, Anhui key laboratory of bioactivity of natural products, Anhui Medical University, Hefei, Anhui Province, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei, Anhui Province, China.
Bin
B
Zhao
School of pharmacy, Anhui key laboratory of bioactivity of natural products, Anhui Medical University, Hefei, Anhui Province, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei, Anhui Province, China.
Cheng
C
Huang
School of pharmacy, Anhui key laboratory of bioactivity of natural products, Anhui Medical University, Hefei, Anhui Province, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei, Anhui Province, China.
Xiao-Ming
XM
Meng
School of pharmacy, Anhui key laboratory of bioactivity of natural products, Anhui Medical University, Hefei, Anhui Province, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei, Anhui Province, China.
Er-Bao
EB
Bian
School of pharmacy, Anhui key laboratory of bioactivity of natural products, Anhui Medical University, Hefei, Anhui Province, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei, Anhui Province, China.
Jun
J
Li
D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D056945:Hep G2 Cells; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008555:Melitten / Q000494:pharmacology*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D025521:Tumor Suppressor Proteins; D008555:Melitten; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D056464:Histone Deacetylase 2