Hinokitiol is a naturally occurring tropolone compound from the Formosan cypress with antibacterial and anticancer properties [1]. Hinokitiol induces oxidative stress, cytotoxicity, and autophagy through modulation of PI3K/Akt/mTOR, p38/ERK/MAPK, nuclear factor kappa B, and c-Jun N-terminal kinase signaling pathways [2]. Hinokitiol has been widely used to inhibit the metabolic processes of bacterial cell membranes, regulate respiration and membrane permeability, thereby effectively killing various bacteria[3].
In vitro, Hinokitiol treatment for 48 hours significantly reduced the cell viability of Ishikawa cells, HEC-1A cells, and KLE cells, with IC50 values of 13.33μM, 49.51μM, and 4.69μM, respectively[4]. Treatment with 30μg/ml Hinokitiol for 24 hours led to the loss of cell membrane integrity and cell cycle arrest in KB-1 cells[5]. Treatment with 40µM Hinokitiol for 24 hours blocked the process of HeLa cells transitioning from the G2/M phase to the G1 phase, increased the expression levels of p21 and p53, promoted cytoplasmic expansion and enhanced SA-β-gal activity, and induced cell senescence[6].
In vivo, Hinokitiol treatment via oral administration at a dose of 100mg/kg every other day for 3 weeks significantly reduced tumor volume and tumor weight in the HCT-116 xenograft mouse model[7]. A single intravenous injection of 1.7mg/kg dose of Hinokitiol can alleviate liver injury induced by hemorrhagic shock/resuscitation in mice within 24 hours[8].
References:
[1] El Hachlafi N, Lakhdar F, Khouchlaa A, et al. Health benefits and pharmacological properties of hinokitiol[J]. Processes, 2021, 9(9): 1680.
[2] Bhuia M S, Chowdhury R, Afroz M, et al. Therapeutic efficacy studies on the Monoterpenoid Hinokitiol in the treatment of different types of cancer[J]. Chemistry & biodiversity, 2025, 22(5): e202401904.
[3] Morita Y, Sakagami Y, Okabe T, et al. The mechanism of the bactericidal activity of hinokitiol[J]. Biocontrol Science, 2007, 12(3): 101-110.
[4] Chen H Y, Cheng W P, Chiang Y F, et al. Hinokitiol exhibits antitumor properties through induction of ROS-mediated apoptosis and p53-driven cell-cycle arrest in endometrial cancer cell lines (Ishikawa, HEC-1A, KLE)[J]. International journal of molecular sciences, 2021, 22(15): 8268.
[5] Roy A, Cheriyan B V, Perumal E, et al. Effect of hinokitiol in ameliorating oral cancer: in vitro and in silico evidences[J]. Odontology, 2025, 113(2): 750-763.
[6] Wang C C, Chen B K, Chen P H, et al. Hinokitiol induces cell death and inhibits epidermal growth factor-induced cell migration and signaling pathways in human cervical adenocarcinoma[J]. Taiwanese Journal of Obstetrics and Gynecology, 2020, 59(5): 698-705.
[7] Lee Y S, Choi K M, Kim W, et al. Hinokitiol inhibits cell growth through induction of S-phase arrest and apoptosis in human colon cancer cells and suppresses tumor growth in a mouse xenograft experiment[J]. Journal of natural products, 2013, 76(12): 2195-2202.
[8] Lu W J, Lin K H, Tseng M F, et al. New therapeutic strategy of hinokitiol in haemorrhagic shock‐induced liver injury[J]. Journal of Cellular and Molecular Medicine, 2019, 23(3): 1723-1734.
Hinokitiol是一种在Formosan cypress中天然存在的tropolone类化合物，具有抗菌和抗癌特性[1]。Hinokitiol通过调控PI3K/Akt/mTOR、p38/ERK/MAPK、核因子κB和c-Jun N-terminal kinase信号通路，诱导氧化应激、细胞毒性和自噬[2]。Hinokitiol已被广泛用于抑制细菌细胞膜的代谢过程，调节呼吸和膜通透性，从而有效杀灭多种细菌[3]。
在体外，Hinokitiol处理Ishikawa细胞、HEC-1A细胞和KLE细胞48小时，显著降低了细胞活力，IC50值分别为13.33μM、49.51μM和4.69μM[4]。30μg/ml的Hinokitiol处理KB-1细胞24小时，导致细胞膜完整性丧失和细胞周期阻滞[5]。40µM的Hinokitiol处理HeLa细胞24小时，阻断了细胞从G2/M期向G1期的转变，增加了p21和p53的表达水平，促进了细胞质扩张并提高了SA-β-gal活性，诱导了细胞衰老[6]。
在体内，每隔一天口服100mg/kg剂量的Hinokitiol，持续3周，显著降低了HCT-116异种移植小鼠模型中的肿瘤体积和肿瘤重量[7]。单次静脉注射1.7mg/kg剂量的Hinokitiol，可在24小时内减轻失血性休克/复苏诱导的小鼠肝损伤[8]。