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Published on: September 12, 2019
Myristoyl-CM4 Exhibits Direct Anticancer Activity and Immune Modulation in Hepatocellular Carcinoma: Evidence from In
Xueli Yuan1, Huidan Zhang1, Yiqiang Zhu1
1Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, Life Sciences College, Nanjing Normal University, 1# Wenyuan Rd., Nanjing 210000, China.
Abstract:
Hepatocellular carcinoma (HCC) is a major clinical challenge due to limited treatment options, More therapy candidates with confirmed anticancer effects are urgently needed. Antimicrobial peptide myristoyl-CM4 exhibits effective anticancer activity against leukemia and breast cancer cells. However, its therapeutic potential in HCC remains unexplored. The objective of the present study was to evaluate the anticancer activity of myristoyl-CM4 against cultured HCC cells and HCC xenograft tumors in mice. Cell viability, apoptosis, proliferation, epithelial-mesenchymal transition, migration, and invasion were assessed using standard assays. Mechanistic studies focused on its effects on macrophages utilized western blotting, immunofluorescence staining, and immunohistochemistry assays in HCC/macrophage co-culture models. The study results showed that myristoyl-CM4 induced apoptosis in HCC cells by targeting mitochondria. It also inhibited HCC cell migration and invasion in both HCC monoculture and HCC/macrophage co-culture systems. Notably, myristoyl-CM4 also promoted M1 macrophage polarization and suppressed M2 polarization in co-culture models both in vitro and in vivo. It also demonstrated effective antitumor activity both in PLC-PRF-5 xenograft and PLC-PRF-5/macrophage co-xenograft mouse models. Collectively, these findings highlighted the therapeutic potential of myristoyl-CM4 in HCC treatment.
Insights
Antimicrobial peptide myristoyl-CM4 shows promise for treating hepatocellular carcinoma (HCC). This study found myristoyl-CM4 effectively reduced HCC tumor growth and spread by inducing cancer cell death and reprogramming immune cells.
Area of Science:
- Oncology
- Immunology
- Biochemistry
Background:
- Hepatocellular carcinoma (HCC) presents a significant clinical challenge with limited therapeutic options.
- Antimicrobial peptides are being explored for anticancer properties, with myristoyl-CM4 showing efficacy in other cancers.
- The therapeutic potential of myristoyl-CM4 in HCC has not been previously investigated.
Purpose of the Study:
- To evaluate the anticancer activity of myristoyl-CM4 against hepatocellular carcinoma (HCC) cells.
- To assess the efficacy of myristoyl-CM4 in HCC xenograft models.
- To investigate the mechanistic effects of myristoyl-CM4 on HCC cells and tumor-associated macrophages.
Main Methods:
- Standard cell-based assays were used to measure cell viability, apoptosis, proliferation, epithelial-mesenchymal transition, migration, and invasion.
- Mechanistic studies involved co-culture models of HCC and macrophages, employing western blotting, immunofluorescence, and immunohistochemistry.
- Antitumor activity was evaluated in PLC-PRF-5 xenograft and co-xenograft mouse models.
Main Results:
- Myristoyl-CM4 induced apoptosis in HCC cells via mitochondrial targeting and inhibited HCC cell migration and invasion.
- The peptide promoted M1 macrophage polarization and suppressed M2 polarization in both in vitro and in vivo co-culture models.
- Significant antitumor activity was observed in both HCC xenograft and co-xenograft mouse models.
Conclusions:
- Myristoyl-CM4 demonstrates potent anticancer effects against hepatocellular carcinoma cells.
- The peptide modulates macrophage polarization, suggesting an immunomodulatory role in HCC treatment.
- Myristoyl-CM4 exhibits significant therapeutic potential for treating hepatocellular carcinoma.
