p53可經由下游因子來達成許多生物功能，例如：細胞週期調控、老化及細胞凋亡……等等。在過去的報告中指出，超過50%的腫瘤細胞其p53存在突變，導致失去其功能；而過去的多項研究也指出，p53可以經由調控p21、PUMA和DRAM等因子來調控許多抑癌反應，故p53被認定為抑癌基因。然而，p53在許多腫瘤中因為人類乳突病毒的E6蛋白作用而導致表現受抑制，尤其是人類子宮頸癌細胞；過去的研究指出，只要在這些非突變細胞中重新活化p53，便能有效抑制癌症生成。我們注意到一種萃取自柏科植物心材的天然物質，扁柏醇，具有潛在的抗癌實力。我們發現扁柏醇可以有效活化p53活性，抑制細胞增生，並在人類子宮頸腺細胞癌HeLa細胞株引發細胞週期停滯、老化等抗癌反應，並誘發自噬作用相關基因表現。此外，我們注意到扁柏醇可以經由抑制相關激酶活性而抑制細胞移行，顯示扁柏醇的抗癌潛力。因此，從它抑制腫瘤增生及移行的特性，我們認為扁柏醇將會是一個有效的抗癌試劑。

P53 and its downstream factors control many biological functions, including aging, cell cycle progression, and cellular death. It is reported that p53 mutates in more than 50% of tumor, and it is found that p53 establishes its anti-tumorgenesis effect by co-operating with various factors, including p21, PUMA, and DRAM, thus it is recognized as tumor suppressor gene. However, human papillomavirus (HPV) infection inactivates p53 through the function of E6 oncoprotein in various cancer cell type, as in human cervical carcinoma cell. Therefore, regeneration of p53 and its function is regarded to be an important strategy to suppress tumorgenesis. In this study, we demonstrated that hinokitiol, a natural compound derived from the heartwood of cupressaceous plants, might limit tumor proliferation. Hinokitiol can reinforce p53 activity in HeLa cervical adenocarcinoma and induce cell cycle arrest, cellular senescence, and autophagic protein expression. Furthermore, hinokitiol also suppresses EGF-induced cellular migration by inhibiting the migration-related kinase activity, indicating the role of hinokitiol in anti-malignancy. Our results suggest that hinokitiol may be a promising reagent to suppress tumor proliferation and migration.

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