Luteolin Impacts on the DNA Damage Pathway in Oral Squamous Cell Carcinoma. - Centre de recherche en cancérologie Nantes-Angers Unité Mixte de Recherche 892 Inserm - 6299 CNRS Accéder directement au contenu
Article Dans Une Revue Nutrition and Cancer Année : 2016

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.

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Cancer
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Dates et versions

inserm-01333887 , version 1 (20-06-2016)

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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, 2016, pp.1-10. ⟨10.1080/01635581.2016.1180411⟩. ⟨inserm-01333887⟩
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