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Eugenol as a potential adjuvant therapy for gingival squamous cell carcinoma
Hawraa Issa1, Lionel Loubaki2, Abdullah Al Amri3
1GREB Research Group, Faculty of Dentistry, Laval University, Québec, Canada.
Abstract:
Adoption of plant-derived compounds for the management of oral cancer is encouraged by the scientific community due to emerging chemoresistance and conventional treatments adverse effects. Considering that very few studies investigated eugenol clinical relevance for gingival carcinoma, we ought to explore its selectivity and performance according to aggressiveness level. For this purpose, non-oncogenic human oral epithelial cells (GMSM-K) were used together with the Tongue (SCC-9) and Gingival (Ca9-22) squamous cell carcinoma lines to assess key tumorigenesis processes. Overall, eugenol inhibited cell proliferation and colony formation while inducing cytotoxicity in cancer cells as compared to normal counterparts. The recorded effect was greater in gingival carcinoma and appears to be mediated through apoptosis induction and promotion of p21/p27/cyclin D1 modulation and subsequent Ca9-22 cell cycle arrest at the G0/G1 phase, in a p53-independent manner. At these levels, distinct genetic profiles were uncovered for both cell lines by QPCR array. Moreover, it seems that our active component limited Ca9-22 and SCC-9 cell migration respectively through MMP1/3 downregulation and stimulation of inactive MMPs complex formation. Finally, Ca9-22 behaviour appears to be mainly modulated by the P38/STAT5/NFkB pathways. In summary, we can disclose that eugenol is cancer selective and that its mediated anti-cancer mechanisms vary according to the cell line with gingival squamous cell carcinoma being more sensitive to this phytotherapy agent.
Insights
Eugenol, a plant compound, shows promise against oral cancer by selectively killing cancer cells and inhibiting tumor growth. It appears more effective against gingival carcinoma, offering a potential phytotherapy approach.
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.
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