Hinokitiol Dysregulates Metabolism of Carcinoma Cell Lines and Induces Downregulation of HPV16E6 and E7 Oncogenes and p21 Upregulation in HPV Positive Cell Lines

Background: Hinokitiol (β-thujaplicin), isolated from the wood of Chamaecyparis taiwanensis, has a wide variety biological properties including anti-inflammatory, anti-microbial, and anti-tumor effects. Therefore, hinokitiol become frequent additive in oral other healthcare products. Objectives: Our goal was to determine activity on human papillomavirus (HPV) positive (n = 3) negative 2) cell lines derived cervical or head neck squamous carcinoma (HNSCC) keratinocyte transformed spontaneously with HPV16E6 E7 oncogenes. Methods: The cell-lines were exposed at different concentrations (0–200 µM) for 24 h. Cell metabolism, proliferation, cycle distribution assessed by MTT- 3H-thymidine incorporation flow cytometry. Expressions p21 oncogenes qPCR. Results: In all lines, treatment declined metabolic irrespective HPV status. This decline statistically significant, however, only HPV-positive CaSki UD-SCC-2 when 100 200 µM, respectively (p < 0.05). Immortalized HMK IHGK, more sensitive as similar effect achieved lower 3.1, 6.25, 50 respectively. blocked DNA synthesis without evident association G1 arrest upregulation found after higher concentration. However, results cells pooled together, increase expression significantly than HPV-negative 0.03), but highest concentration (200 µM). HPV16E7 E6 along expression. dose-dependent inverse correlation between significant SiHa (r −0.975, p-value 0.03) borderline −0.944, 0.06), which also inversely correlated −0.989). Conclusions: indicate that might have potential preventing progress immortalized toward malignancy growth malignant lesions. can influence progression HPV-associated lesions downregulating