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Anti-metastasis traditional Chinese medicine monomer screening system based on perinucleolar compartment analysis in
Feifei Liu1, Guohua Lou1, Tianbao Zhang1
1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou 310003, China.
Abstract:
Hepatocellular Carcinoma (HCC) lacks effective anti-metastasis drugs. Traditional Chinese Medicine (TCM) monomers have shown anti-proliferation activity in HCC, but few of them are specifically anti-metastasis. Therefore, further clarifying the indicators of HCC metastasis and screening TCM monomers based on the indicators, will effectively guide the development of novel anti-HCC drugs. The perinucleolar compartment (PNC), existing in the nuclear of tumor cells, is closely correlated with metastasis of several tumors. In this study, we found positive correlation between higher PNC prevalence and metastasis in HCC tissue of patients. The PNC prevalence was also positively correlated with the malignancy of HCC cell lines. On this premise, we established a PNC-based screening system for anti-metastasis TCM monomers and obtained Camptothecin (CPT), Evodiamine and Isoglycyrrhizin, the three most effective TCM monomers from a TCM monomer library to reduce the PNC prevalence in Huh7 cells. The anti-metastasis effect of these TCM monomers was positively correlated with their PNC inhibitor effect. Our data further revealed that CPT reduced metastasis of Huh7 cells possibly by inhibiting Epithelial-Mesenchymal Transition by upregulating the expression of ZO-1, E-cadherin and Claudin-1. The PNC-based screening system is effective and it may provide an effective technical platform for the development of anti-metastasis drugs.
Insights
Hepatocellular carcinoma (HCC) metastasis is linked to the perinucleolar compartment (PNC). Researchers developed a PNC-based system to screen Traditional Chinese Medicine monomers, identifying effective anti-metastasis compounds.
Area of Science:
- Oncology
- Cell Biology
- Pharmacology
Background:
- Hepatocellular Carcinoma (HCC) presents a significant challenge due to the lack of effective anti-metastasis drugs.
- Traditional Chinese Medicine (TCM) monomers show anti-proliferation effects, but specific anti-metastasis agents are scarce.
- The perinucleolar compartment (PNC) is a nuclear structure implicated in tumor metastasis.
Purpose of the Study:
- To investigate the correlation between PNC prevalence and HCC metastasis.
- To establish a screening system for anti-metastasis TCM monomers based on PNC inhibition.
- To identify effective TCM monomers for inhibiting HCC metastasis.
Main Methods:
- Correlation analysis of PNC prevalence with HCC patient metastasis and cell line malignancy.
- Development of a PNC-based screening system using Huh7 cells.
- Screening of a TCM monomer library to identify compounds reducing PNC prevalence.
Main Results:
- A positive correlation was observed between higher PNC prevalence and metastasis in HCC tissues and cell lines.
- Camptothecin (CPT), Evodiamine, and Isoglycyrrhizin were identified as effective PNC inhibitors.
- The anti-metastatic efficacy of these TCM monomers correlated with their PNC inhibitory activity.
- CPT demonstrated potential to inhibit Epithelial-Mesenchymal Transition (EMT) by upregulating ZO-1, E-cadherin, and Claudin-1.
Conclusions:
- The PNC is a potential indicator for HCC metastasis.
- A novel PNC-based screening system is effective for identifying anti-metastasis TCM monomers.
- This system offers a promising platform for developing new anti-HCC metastasis drugs.
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