Eugenol as a potential adjuvant therapy for gingiva carcinoma
Hawraa Issa1, Lionel Loubaki2, Abdullah Al Amri3, Kazem Zibara4, Mahmoud Rouabhia1Mikhlid Almutairi3 and Abdelhabib Semlali1*
1GREB research group, Faculty of Dentistry, Laval University, Québec, Canada, 2Héma-Québec, Medical affairs and innovation, Québec, Canada, 3College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia, 4PRASE and Biology Department, Faculty of Sciences - I, Lebanese University, Beirut, Lebanon
Background. Oral cancer incidence and mortality are rising worldwide with squamous cell carcinoma accounting for the grand majority of cases and tongue carcinoma being considered among the most aggressive forms. Often diagnosed at a late stage, the prognosis of oral tumors remains bleak despite therapeutic management with surgery, radiotherapy and chemotherapy. Thus, the current focus is leaning towards plant-derived compounds as they are shown to be cheaper, effective while exhibiting reduced adverse effects. Eugenol, found in plants, has been acknowledged for its anti-cancer effects in multiple models. However, very few studies investigated drug clinical relevance for gingiva carcinoma. Purpose. We ought to explore Eugenol effectiveness in vitro while confirming tumor selectivity and comportment according to aggressiveness level. Methods. Non-oncogenic human oral epithelial cells (GMSM-K) were used together with the Tongue (SCC-9) and Gingiva (Ca9-22) squamous cell carcinoma lines to assess key tumorigenesis processes.
Results. Eugenol inhibited cell proliferation and colony formation while inducing cytotoxicity in cancer cells as compared to normal counterparts. The recorded effect was greater in gingiva 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.
Conclusion. We can disclose that Eugenol-mediated anti-cancer mechanisms vary according to the cell line with gingiva squamous cell carcinoma being more sensitive to this phytotherapy agent.
Keywords. Oral cancer, gingiva and tongue carcinomas, Eugenol, phytotherapy, tumorigenesis.