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Published on: July 17, 2020
Melittin induces PTCH1 expression by down-regulating MeCP2 in human hepatocellular carcinoma SMMC-7721 cells
Xiaoqin Wu1, Bin Zhao1, Yahui Cheng1
1School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; The Key Laboratory of Anti-inflammatory and Immune Medicine, Anhui Medical University, Ministry of Education, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University, ILD-AMU, Anhui Medical University, Hefei 230032, China.
Abstract:
Hepatocellular carcinoma (HCC) has a high mortality rate worldwide and still remains to be a noticeable public health problem. Therefore, new remedies are urgently needed. Melittin, a major component of bee venom, is known to suppress cell growth in various cancers including HCC. However, the mechanism of the anticancer effect of melittin on HCC has not been fully elucidated. It has been reported that Methyl-CpG binding protein 2 (MeCP2) plays a key role in tumor proliferation, apoptosis, migration and invasion. In the present study, we found the high expression of MeCP2 in human HCC tissues and in the SMMC-7721 cell line. MeCP2 silencing inhibited cell proliferation, while over-expression of MeCP2 promoted cell growth in SMMC-7721 cells. It indicates that MeCP2 may be an attractive target for human HCC. We further found that melittin could inhibit cell proliferation by reducing MeCP2 expression in vitro. Interestingly, the inhibitory effect of melittin on cell proliferation was due to a delay in G0/G1 cell cycle progression, without influencing cell apoptosis. Next, we investigated the potential molecular mechanisms and found that MeCP2 could modulate Shh signaling in SMMC-7721 cells. Further study indicates that melittin may induce the demethylation of PTCH1 promoter, resulting in the increased expression of PTCH1. Furthermore, the expression of Shh and GLI1 was significantly lowered upon treatment of melittin. These results suggest that melittin can block Shh signaling in vitro. In short, these results indicate that melittin inhibits cell proliferation by down-regulating MeCP2 through Shh signaling in SMMC-7721 cells.
Insights
Melittin, a bee venom component, inhibits hepatocellular carcinoma (HCC) growth by reducing Methyl-CpG binding protein 2 (MeCP2) expression. This mechanism involves blocking the Shh signaling pathway, offering a potential new therapy for HCC.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Hepatocellular carcinoma (HCC) presents a significant global health challenge with high mortality rates.
- Existing treatments for HCC are limited, necessitating the exploration of novel therapeutic agents.
- Melittin, derived from bee venom, exhibits anticancer properties, but its precise mechanism in HCC remains unclear.
Purpose of the Study:
- To investigate the role of Methyl-CpG binding protein 2 (MeCP2) in HCC proliferation and its modulation by melittin.
- To elucidate the molecular mechanisms underlying melittin's anticancer effects in HCC.
- To explore the potential of targeting MeCP2 and Shh signaling for HCC treatment.
Main Methods:
- Analysis of MeCP2 expression in human HCC tissues and cell lines.
- In vitro studies involving MeCP2 silencing and overexpression in SMMC-7721 cells.
- Treatment of SMMC-7721 cells with melittin to assess its effects on cell proliferation, cell cycle, apoptosis, and signaling pathways.
- Investigation of melittin's impact on MeCP2 expression, PTCH1 promoter methylation, and Shh signaling components (Shh, GLI1).
Main Results:
- MeCP2 was highly expressed in HCC tissues and cells, promoting proliferation.
- Melittin inhibited HCC cell proliferation by down-regulating MeCP2 expression and causing G0/G1 cell cycle arrest.
- Melittin suppressed Shh signaling by potentially inducing PTCH1 promoter demethylation, leading to decreased Shh and GLI1 expression.
- Melittin's inhibitory effect on proliferation was independent of apoptosis induction.
Conclusions:
- MeCP2 is a key driver of HCC proliferation and a potential therapeutic target.
- Melittin effectively inhibits HCC cell proliferation in vitro by down-regulating MeCP2.
- Melittin exerts its anticancer effects through the inhibition of the Shh signaling pathway.
- These findings suggest melittin as a promising candidate for novel HCC therapies targeting MeCP2 and Shh signaling.
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