Hinokitiol suppressed pan-histone expression and cell growth in oral squamous cell carcinoma cells

• Hinokitiol exhibited more cytotoxicity to OSCC cells than normal oral cells.
• Hinokitiol decreased pan-histone expression and impaired chromatin folding.
• Hinokitiol downregulated pan-histone expression by inhibiting the transcription.
• Hinokitiol suppressed the malignant phenotypes in vitro and tumourigenicity in vivo.

Hinokitiol is reported to inhibit oral squamous cell carcinoma cells growth but its mechanism of action remains unclear. Hinokitiol induced cell cycle arrest in G1 or G1/S phase and induced cell apoptosis in oral squamous cell carcinoma cells. The cDNA microarray data showed 6.25–12.5 µM hinokitiol suppressed pan-histone mRNA expression and quantitative RT-PCR and western blotting showed the reproducibility of the results. Hinokitiol impaired the chromatin folding in oral squamous cell carcinoma cells. In addition, the binding of FLICE-associated huge protein and nuclear protein of the ataxia telangiectasia mutated locus on histone H4/e promoter was decreased, and H4/e promoter activity was significantly decreased. The malignant phenotypes of oral squamous cell carcinoma cells were suppressed in low dose (0.75–6.25 µM hinokitiol) in vitro. Feeding 10 mg/kg hinokitiol to mice suppressed xenograft tumourigenicity of HSC-3 cells in vivo. Hinokitiol showed the efficacy against oral squamous cell carcinoma cells growth by pan-histone suppression.

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