Luteolin Impacts on the DNA Damage Pathway in Oral Squamous Cell Carcinoma.
Résumé
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.
Domaines
Cancer
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