Luteolin Impacts on the DNA Damage Pathway in Oral Squamous Cell Carcinoma. - Archive ouverte HAL Access content directly
Journal Articles Nutrition and Cancer Year : 2016

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

(1, 2) , (2) , (1, 3)
1
2
3

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.
Embargoed file
Embargoed file
Ne sera jamais visible
Loading...

Dates and versions

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

Identifiers

Cite

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⟩
114 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More