Luteolin Impacts on the DNA Damage Pathway in Oral Squamous Cell Carcinoma.
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.
a Institut Cochin, CNRS, INSERM, Universite Paris Descartes , Paris , France.|b Department of Stomatology , Area of Pathology, Bauru School of Dentistry, University of Sao Paulo , Bauru , Sao Paulo , Brazil.
Kellen Cristine
KC
Tjioe
b Department of Stomatology , Area of Pathology, Bauru School of Dentistry, University of Sao Paulo , Bauru , Sao Paulo , Brazil.
Denise
D
Tostes Oliveira
a Institut Cochin, CNRS, INSERM, Universite Paris Descartes , Paris , France.|c CRCNA, CNRS, INSERM, Universite de Nantes-Angers , Nantes , France.|d Team SOAP, Signaling in Oncogenesis, Angiogenesis, and Permeability , Nantes , France.
Julie
J
Gavard
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006801:Humans; D047311:Luteolin / Q000494:pharmacology*; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000473:pathology*; D009574:Nitro Compounds; D013844:Thiazoles / Q000494:pharmacology; D013892:Thioxanthenes / Q000494:pharmacology; D020032:Tyrphostins / Q000494:pharmacology
D000970:Antineoplastic Agents; D009574:Nitro Compounds; D013844:Thiazoles; D013892:Thioxanthenes; D020032:Tyrphostins; C005111:methixene; D047311:Luteolin; D002945:Cisplatin; C041747:nitazoxanide