Pharmacological mechanisms of norcantharidin against hepatocellular carcinoma
Zhong-Ming Qian1,2, Yun-Jin Chen1,2, Yu-Xin Bao3
1Institute of Translational and Precision Medicine, Department of Neurology, Affiliated Hospital, Nantong University No. 19 Qi Xiu Road, Nantong 226001, Jiangsu, China.
Abstract:
Norcantharidin (NCTD) is a water-soluble synthetic small molecule drug that has been approved by the Chinese FDA for the treatment of cancer in China. Among these NCTD-treated cancers, hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide and one of the most extensively studied. Research over the past few decades has made great strides in understanding how NCTD induces mitotic arrest, anti-proliferation, anti-metastasis, apoptosis and cytotoxic autophagy or autophagic cell death in HCC. In this article, we review recent progress in the application of NCTD for the treatment of HCC, with emphasis on the pharmacological mechanism of NCTD against hepatocellular carcinoma. The accumulated results show that NCTD has the ability to induce mitotic arrest, anti-proliferation, anti-metastasis, apoptosis and cytotoxic autophagy or autophagic cell death in HCC by down-regulating the expression of ISG15, MMP-9, u-PA, Mcl-1 and the accumulation of regulatory T cells, up-regulating the expression of FAM46C, miR-214 and the expression and phosphorylation of p21Cip1/Waf1 and CDC25C, and by inhibiting the c-Met-mTOR and JAK/STAT3 signaling pathways, reversing the methylation of RASSF1A gene, and activating TRAIL-R2/DR5 signal transduction.
Insights
Norcantharidin (NCTD) effectively treats hepatocellular carcinoma (HCC) by inducing cell death and inhibiting proliferation and metastasis. Its mechanisms involve regulating key genes and signaling pathways, offering a promising therapeutic strategy for HCC.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Hepatocellular carcinoma (HCC) is a major global health concern.
- Norcantharidin (NCTD) is an approved anti-cancer drug in China, particularly studied for HCC treatment.
Purpose of the Study:
- To review the recent advancements in NCTD application for HCC treatment.
- To elucidate the pharmacological mechanisms of NCTD against HCC.
Main Methods:
- Review of research on NCTD's effects on HCC.
- Analysis of NCTD's impact on cellular processes like mitotic arrest, proliferation, metastasis, and cell death.
- Investigation of NCTD's molecular targets and signaling pathways.
Main Results:
- NCTD induces mitotic arrest, anti-proliferation, anti-metastasis, apoptosis, and cytotoxic autophagy in HCC.
- Mechanisms include down-regulation of ISG15, MMP-9, u-PA, Mcl-1, and regulatory T cells.
- Upregulation of FAM46C, miR-214, p21Cip1/Waf1, and CDC25C, alongside inhibition of c-Met-mTOR and JAK/STAT3 pathways.
Conclusions:
- NCTD exhibits multifaceted anti-HCC properties through diverse molecular pathways.
- NCTD demonstrates significant potential as a therapeutic agent for hepatocellular carcinoma.
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