Hispolon induces apoptosis in oral squamous cell carcinoma cells through JNK/HO-1 pathway activation

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Oral squamous cell carcinoma (OSCC) presents significant challenges due to high recurrence and poor patient outcomes.
• Hispolon, a natural polyphenol, exhibits promising antiviral, antioxidant, and anticancer properties, suggesting its therapeutic potential.
• The precise anticancer mechanisms of hispolon in OSCC remain largely unexplored, necessitating further investigation.

Purpose of the Study:

• To elucidate the apoptosis-inducing effects and underlying molecular mechanisms of hispolon in OSCC cells.
• To investigate the role of specific signaling pathways, including mitogen-activated protein kinases (MAPKs), in hispolon-mediated apoptosis.
• To evaluate the potential of hispolon as a chemotherapeutic agent for oral cancer.

Main Methods:

• Cell viability and clonogenic assays were employed to assess hispolon's impact on OSCC cell proliferation.
• Fluorescent nuclear staining and flow cytometry were used to quantify apoptosis induction.
• Proteome profiling via a human apoptosis array identified key protein expression changes, including heme oxygenase-1 (HO-1).
• Caspase activity and MAPK pathway involvement (JNK, ERK, p38) were analyzed through co-treatment experiments with specific inhibitors.

Main Results:

• Hispolon treatment significantly induced apoptosis in OSCC cells, evidenced by upregulated cleaved caspase-3, -8, and -9, and downregulated cellular inhibitor of apoptosis protein-1 (cIAP1).
• Overexpression of heme oxygenase-1 (HO-1) was observed, indicating its involvement in hispolon-induced caspase-dependent apoptosis.
• Hispolon selectively activated the c-Jun N-terminal kinase (JNK) pathway, but not the extracellular signal-regulated kinase (ERK) or p38 pathways, in inducing apoptosis.

Conclusions:

• Hispolon demonstrates significant anticancer effects against oral squamous cell carcinoma by promoting caspase-dependent apoptosis.
• The JNK pathway activation and HO-1 upregulation are critical mechanisms mediating hispolon's anti-OSCC activity.
• Hispolon represents a promising candidate for developing novel therapeutic strategies against oral cancer.