Cetylpyridinium chloride (CPC), a quaternary ammonium surfactant with broad-spectrum antimicrobial activity, has demonstrated promising anti-tumor activity against hepatocellular carcinoma (HCC), the most common form of primary liver cancer. Researchers have found that CPC inhibits the proliferation, invasion, and metastasis of HCC cells both in vitro and in vivo, suggesting its potential as a therapeutic agent for liver cancer. The study, published in PLOS ONE, highlights CPC's ability to induce apoptosis and suppress epithelial-mesenchymal transition (EMT) in HCC cells. Given the limited treatment options for advanced HCC and the challenges of drug resistance, these findings offer a potential new avenue for HCC treatment.
CPC Inhibits HCC Cell Proliferation and Induces Apoptosis
In vitro experiments revealed that CPC significantly inhibits the proliferation of HCC cells in a dose- and time-dependent manner. The IC50 values for CPC in various cancer cell lines ranged from 1.84 to 2.91 μM, while normal cell lines showed IC50 values from 7.12 to 8.83 μM, indicating that cancer cells are more sensitive to CPC. Colony formation assays further confirmed that CPC treatment significantly reduced the colony-forming ability of HCC cell lines. Flow cytometry analysis demonstrated that CPC promotes apoptosis in HCC cells by increasing the expression of pro-apoptotic proteins such as cleaved-caspase-3, Bax, and p53, while inhibiting the expression of the anti-apoptotic protein Bcl-xL.
CPC Suppresses Migration and Invasion by Regulating EMT
The study also investigated the effect of CPC on the migration and invasive capacity of HCC cells. Wound-healing assays and transwell assays showed that CPC significantly inhibited the migration and invasion of HCC cells in a dose-dependent manner. Mechanistically, CPC was found to regulate EMT by enhancing the expression of the epithelial marker E-cadherin and inhibiting the expression of mesenchymal markers such as Slug, N-cadherin, and Vimentin. These findings suggest that CPC inhibits HCC invasion and metastasis by reversing the EMT process.
In Vivo Efficacy Against HCC Tumor Growth and Metastasis
To validate the in vitro findings, in vivo experiments were conducted using xenograft mouse models. The results showed that CPC effectively suppressed HCC tumor growth without affecting the body weight of the mice. Consistent with the in vitro results, CPC regulated EMT-related proteins and promoted apoptosis in tumor tissues. Furthermore, using a nude mouse metastasis model, CPC significantly inhibited the lung metastasis of HCC cells. These in vivo data provide strong evidence for the therapeutic potential of CPC in treating HCC.
Implications for HCC Treatment
HCC is a major global health burden, with limited effective treatment options for advanced stages. The current standard treatments, such as sorafenib and doxorubicin, often face challenges of drug resistance and toxic side effects. The discovery of CPC's anti-tumor activity against HCC offers a promising new approach. "Our investigation showed that CPC significantly inhibited HCC cell proliferation, invasion and metastasis in vivo and in vitro, by inducing the expression of apoptosis-related genes and inhibiting expression of EMT markers, suggesting that CPC is a potential agent for HCC treatment," the researchers stated. Further studies are warranted to explore the clinical potential of CPC in HCC treatment.
