Eugenol as a potential adjuvant therapy for gingival squamous cell carcinoma

Area of Science:

• Oncology
• Phytochemistry
• Molecular Biology

Background:

• Growing chemoresistance and side effects of conventional oral cancer treatments necessitate novel therapeutic strategies.
• Plant-derived compounds, like eugenol, are gaining attention for their potential anti-cancer properties.
• Limited research exists on eugenol's efficacy specifically for gingival carcinoma.

Purpose of the Study:

• To investigate the selectivity and anti-cancer mechanisms of eugenol in oral squamous cell carcinoma.
• To compare eugenol's effects on different oral cancer cell lines based on aggressiveness.
• To explore eugenol's impact on key tumorigenesis processes, including cell proliferation, apoptosis, cell cycle, and migration.

Main Methods:

• Utilized non-oncogenic human oral epithelial cells (GMSM-K) and oral squamous cell carcinoma lines (SCC-9, Ca9-22).
• Assessed eugenol's effects on cell proliferation, colony formation, and cytotoxicity.
• Analyzed apoptosis induction, cell cycle arrest (p53-independent), gene expression (QPCR array), and cell migration (MMP1/3).
• Investigated signaling pathways (P38/STAT5/NFkB) involved in Ca9-22 cell behavior.

Main Results:

• Eugenol inhibited proliferation and colony formation while inducing cytotoxicity in cancer cells, sparing normal cells.
• Greater efficacy was observed in gingival carcinoma (Ca9-22) compared to tongue carcinoma (SCC-9).
• Eugenol-induced apoptosis and cell cycle arrest (G0/G1 phase) in Ca9-22 cells via p21/p27/cyclin D1 modulation.
• Eugenol modulated cell migration by downregulating MMP1/3 in Ca9-22 and affecting MMPs in SCC-9.
• Ca9-22 cell behavior was significantly influenced by P38/STAT5/NFkB pathways.

Conclusions:

• Eugenol demonstrates cancer selectivity, acting as a potential phytotherapy agent for oral cancer.
• The anti-cancer mechanisms of eugenol vary depending on the specific oral cancer cell line.
• Gingival squamous cell carcinoma exhibits higher sensitivity to eugenol compared to other oral cancer types studied.