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.

Inhibition of mTOR in head and neck cancer cells alters endothelial cell morphology in a paracrine fashion

“…Human oral cavity squamous cell carcinoma‐derived cell line HN26, human pharyngeal squamous cell carcinoma‐derived cell line HN30, and immortalized Human Umbilical Vein Endothelial‐derived cell line HUVEC (ea.hy526 cells, ATCC) were grown in Dulbecco's modified Eagle's medium (DMEM, Life Technologies, Courtaboeuf, France) supplemented with 10% fetal bovine serum (FBS, Life Technologies), GlutaMAX, and antibiotics (Life Technologies). Cell lines were expanded in a humidified atmosphere of 5% CO2 at 37°C.…”

“…Human oral cavity squamous cell carcinoma-derived cell line HN26, 8 human pharyngeal squamous cell carcinoma-derived cell line HN30, 8…”

“…Cell viability was evaluated using MTT assay (1-[4,5-dimethylthiazol-2-yl]-3,5-diphenylformazan, thiazolyl blue formazan; Sigma-Aldrich), as described previously. 8 Cells were cultivated in a 96-well plate in triplicate at a density of 2.5 × 10 3 per well and treatments administered 12 h after plating. Twenty-four hours post-drug challenge, cells were incubated with MTT (5 mg/mL) for 4 h to allow the formation of formazan crystals.…”

Plant-Derived Natural Products in Cancer Research: Extraction, Mechanism of Action, and Drug Formulation

“…Kasala et al confirmed the antioxidant and antitumor activities of luteolin against benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice [257]. Tjioe et al identified luteolin as a potent cytotoxic drug against oral squamous cell carcinoma with low toxicity and high efficiency [258]. It remains to mention that chemopreventive and chemotherapeutic effects of luteolin are also contributed to the synergistic effects with other anticancer therapies such as cyclophosphamide, doxorubicin, and NSAID such as celecoxib [259,260].…”

Inhibitory Growth of Oral Squamous Cell Carcinoma Cancer via Bacterial Prodigiosin

“…Nonetheless, these chemotherapy drugs always induce side effects, such as nausea, vomiting, loss of appetite, decreased immunity, and adverse effects of oral ulcers. Recently, many natural sources [ 33 , 34 , 35 , 36 , 37 ] and traditional medicinal herbs [ 38 , 39 , 40 ] have been studied on OSCC in an effort to mitigate the abovementioned problems, however the solicitation remains incompletely explored. The present study investigated whether PG could have benefits to cause the inhibiting growth of human gingival squamous carcinoma cells (OECM-1) and human tongue cancer (SAS) cell lines by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry assay, Western blotting and autophagosome formation assay.…”