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Published on: July 17, 2020
Melittin restores PTEN expression by down-regulating HDAC2 in human hepatocelluar carcinoma HepG2 cells
Hui Zhang1, Bin Zhao1, Cheng Huang1
1School 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.
Abstract:
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.
Insights
Melittin inhibits liver cancer cell growth by downregulating CyclinD1 and CDK4. It also upregulates PTEN and inactivates Akt via histone deacetylase 2 (HDAC2), blocking PI3K/Akt signaling.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Melittin, a peptide from bee venom, exhibits anti-tumor properties in various cancers, but its precise mechanisms, especially in liver cancer, are not fully understood.
- Hepatocellular carcinoma (HCC) remains a significant global health challenge, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the anti-proliferative effects of melittin on human hepatocellular carcinoma HepG2 cells in vitro.
- To elucidate the molecular mechanisms underlying melittin's anti-cancer activity, focusing on cell cycle regulators and signaling pathways.
Main Methods:
- Cell proliferation was assessed using Flow cytometry and MTT assays.
- Gene and protein expression levels were analyzed via Real-time PCR and Western Blot.
- Gene knockdown and overexpression techniques were employed to study the role of histone deacetylase 2 (HDAC2).
Main Results:
- Melittin significantly inhibited HepG2 cell proliferation.
- Melittin downregulated the expression of CyclinD1 and CDK4, key cell cycle regulators.
- Melittin upregulated PTEN expression and downregulated HDAC2 expression.
- HDAC2 knockdown mimicked melittin's effect on PTEN, while HDAC2 overexpression reversed it.
- Melittin treatment led to decreased Akt phosphorylation, indicating Akt pathway inactivation.
Conclusions:
- Melittin exerts anti-proliferative effects on HepG2 cells by inhibiting cell cycle progression.
- The mechanism involves HDAC2-mediated upregulation of PTEN and subsequent inactivation of the PI3K/Akt signaling pathway.
- Melittin shows potential as a therapeutic agent for hepatocellular carcinoma.
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