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

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.
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Submitted on : Monday, June 20, 2016 - 10:05:43 AM
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Kellen Cristine Tjioe, Denise Tostes Oliveira, Julie Gavard. Luteolin Impacts on the DNA Damage Pathway in Oral Squamous Cell Carcinoma.. Nutrition and Cancer, Taylor & Francis (Routledge), 2016, pp.1-10. ⟨10.1080/01635581.2016.1180411⟩. ⟨inserm-01333887⟩



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