ABSTRACT
Oral squamous cell carcinoma (OSCC) exhibited high chemoresistance to current treatments. Here we aimed at identifying and repositioning approved drugs that could be selectively toxic toward OSCC cells. Through a cell-based drug screening of 1,280 chemical molecules, we selected compounds lethal to oral cancer SCC-25 cells, while sparing normal keratinocyte HaCaT cells. Within the chemical library, the natural flavonoid luteolin was identified as a potent cytotoxic agent against oral cancer cells in vitro, along with metixene hydrochloride and nitazoxanide. Of note, they exhibit low toxicity and high efficiency compared to the standard-of-care, such as cisplatin and the epidermal growth factor receptor inhibitor tyrphostin. From a molecular standpoint, luteolin causes phosphorylation of ataxia telangiectasia mutated (ATM) and H2AX in a DNA repair pathway and can be efficiently combined with a checkpoint kinase (CHK) pharmacological inhibitor. Thus, luteolin emerges as a potent cytotoxic and/or adjuvant therapy in oral cancer, as it is a natural compound presenting better effects in vitro compared to conventional chemotherapeutic agents. Future in vivo exploration is next required to provide the proof-of-concept that luteolin could be an efficient anticancer molecule.
Acknowledgments
We would like to thank the past and present members of SOAP Team laboratory, especially Nicolas Bidère and Eva Galan-Moya.
Funding
This research was funded by Fondation pour la Recherche Medicale, Institut National du Cancer INCA_6508, Ligue nationale contre le cancer comite de Loire-Atlantique and Sarthe, Region Pays-de-la-Loire, Nantes Metropole, and Coordenaçao de Aperfeicoamento de Pessoal de Nivel Superior (#2788-13-6).