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

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Oral squamous cell carcinoma (OSCC) presents significant chemoresistance to existing therapies.
• There is a critical need for novel therapeutic strategies and drug repositioning for OSCC.
• Identifying selectively toxic agents for OSCC is a key research objective.

Purpose of the Study:

• To identify and reposition approved drugs with selective toxicity against OSCC cells.
• To evaluate the efficacy and safety of identified compounds compared to standard treatments.
• To elucidate the molecular mechanisms of action for promising drug candidates.

Main Methods:

• A cell-based drug screening of 1,280 chemical molecules was performed.
• Compounds were tested for selective lethality against OSCC SCC-25 cells versus normal HaCaT keratinocytes.
• Molecular analysis focused on DNA repair pathways, including ATM and H2AX phosphorylation.

Main Results:

• Luteolin, metixene hydrochloride, and nitazoxanide were identified as potent cytotoxic agents against OSCC cells.
• Luteolin demonstrated superior in vitro efficacy and lower toxicity compared to cisplatin and tyrphostin.
• Luteolin induced phosphorylation of ATM and H2AX, suggesting DNA damage pathway activation.

Conclusions:

• Luteolin is a promising natural compound for oral cancer therapy, exhibiting potent in vitro cytotoxicity and potential as an adjuvant treatment.
• The identified drugs, particularly luteolin, offer a potential alternative or adjunct to conventional chemotherapies for OSCC.
• Further in vivo studies are warranted to validate luteolin's efficacy as an anticancer agent.