Ailanthone (δ13-Dehydrochaparrinone), a quassinoid extract from the traditional Chinese medicine plant Ailanthus altissima, is a potent inhibitor of both full-length androgen receptor (AR) (IC50=69nM) and constitutively active truncated AR splice variants (AR-Vs IC50=309nM)[1]. The androgen receptor (AR) is a ligand-dependent nuclear receptor that, upon stimulation by testosterone or dihydrotestosterone, transcriptionally regulates genes essential for prostate development and function,while AR-Vs lack the ligand-binding domain and sustain AR signaling even in the absence of androgens, thereby driving cancer progression[2]. Ailanthone (δ13-Dehydrochaparrinone) is widely used in various cancer researches[3].
In vitro, treatment of human Huh7 hepatocellular carcinoma cells with Ailanthone (δ13-Dehydrochaparrinone) (0, 0.2, 0.4 or 0.8μM for 0, 36h, 48h, or 60h)inhibits cell proliferation in a concentration- and time-dependent manner, induces G0/G1 cell-cycle arrest and DNA damage, triggers activation of the ATM/ATR pathway, and elicits caspase-dependent mitochondrial apoptosis[4]. Ailanthone (δ13-Dehydrochaparrinone) (0.1–0.8μM; 48h) dose-dependently inhibits the proliferation of human melanoma cell lines SK-MEL-5, SK-MEL-28, A375 and WM35, induces c-Jun degradation, and suppresses PD-L1 transcription[5].
In vivo, Ailanthone (δ13-Dehydrochaparrinone) (5mg/kg; i.p. qod; 20 days) reversed bleomycin-induced pulmonary fibrosis in mice, reduced collagen deposition and lung hydroxyproline content, and restored the lung function parameter Penh to normal levels[6]. Ailanthone (δ13-Dehydrochaparrinone) (2mg/kg; i.p.; every 3 days for 30 days) reduced the number of lung metastatic nodules in Saos-2 osteosarcoma mice from 31 to 8 and markedly down-regulated KMT2A, MEN1, PHGDH, PSAT1 and PSPH proteins in metastatic lung tissues[7].
References:
[1] He Y, Peng S, Wang J, et al. Ailanthone targets p23 to overcome MDV3100 resistance in castration-resistant prostate cancer. Nat Commun. 2016;7:13122.
[2] Kato M, Banuelos CA, Imamura Y, et al. Cotargeting Androgen Receptor Splice Variants and mTOR Signaling Pathway for the Treatment of Castration-Resistant Prostate Cancer. Clin Cancer Res. 2016;22(11):2744-2754.
[3] Ding H, Yu X, Hang C, et al. Ailanthone: A novel potential drug for treating human cancer. Oncol Lett. 2020;20(2):1489-1503.
[4] Zhuo Z, Hu J, Yang X, et al. Ailanthone Inhibits Huh7 Cancer Cell Growth via Cell Cycle Arrest and Apoptosis In Vitro and In Vivo. Sci Rep. 2015;5:16185.
[5] Yu P, Wei H, Li K, et al. The traditional chinese medicine monomer Ailanthone improves the therapeutic efficacy of anti-PD-L1 in melanoma cells by targeting c-Jun. J Exp Clin Cancer Res. 2022;41(1):346.
[6] Zhao L, Zhu Y, Tao H, et al. Ailanthone ameliorates pulmonary fibrosis by suppressing JUN-dependent MEOX1 activation. Acta Pharm Sin B. 2024;14(8):3543-3560.
[7] Liang J, Qiao G, Zhang Y, et al. Ailanthone targets the KMT2A-MEN1 complex to suppress lung metastasis of osteosarcoma. Phytomedicine. 2025;136:156258.
Ailanthone (δ13-Dehydrochaparrinone)是一种源自传统中药植物臭椿（Ailanthus altissima）的苦木素类化合物，是全长雄激素受体（AR）（IC50=69nM）及其组成型活性截短剪接变体（AR-Vs）（IC50=309nM）的强效抑制剂[1]。雄激素受体（AR）是一种依赖配体的核受体，在睾酮或二氢睾酮刺激下，通过转录调控前列腺发育与功能相关基因；而AR-Vs缺乏配体结合结构域，可在无雄激素条件下持续激活AR信号通路，从而驱动癌症进展[2]。Ailanthone (δ13-Dehydrochaparrinone)被广泛应用于多种癌症研究[3]。
体外实验中，Ailanthone (δ13-Dehydrochaparrinone)（0.2、0.4或0.8μM，作用0、36、48或60小时）可浓度-和时间依赖性地抑制人Huh7肝细胞癌细胞的增殖，诱导G0/G1期细胞周期阻滞和DNA损伤，激活ATM/ATR通路，并触发半胱天冬酶依赖性线粒体凋亡[4]。Ailanthone (δ13-Dehydrochaparrinone)(0.1–0.8μM; 48小时) 剂量依赖性地抑制人黑色素瘤细胞系SK-MEL-5、SK-MEL-28、A375及WM35的增殖，诱导c-Jun降解并抑制PD-L1转录[5]。
体内实验中，Ailanthone (δ13-Dehydrochaparrinone)（5mg/kg；隔日腹腔注射；持续20天）逆转了博来霉素诱导的小鼠肺纤维化，减少胶原沉积及肺羟脯氨酸含量，并将肺功能参数Penh恢复至正常水平[6]。Ailanthone (δ13-Dehydrochaparrinone)（2mg/kg；腹腔注射；每3天一次，共30天）使Saos-2骨肉瘤小鼠肺转移结节数由31个降至8个，并显著下调转移肺组织中的KMT2A、MEN1、PHGDH、PSAT1和PSPH蛋白表达[7]。