Gambogenic acid, the main active component of gamboge, inhibits Aurora A kinase, with an IC50 value of 1.425μM[1]. Gambogenic acid triggers endoplasmic reticulum (ER) stress-mediated apoptosis through the reactive oxygen species/IRE1α/c-Jun N-terminal kinase signalling pathway[2]. Gambogenic acid has been widely used as an anticancer agent to inhibit the growth of different cancer cells[3].
In vitro, Gambogenic acid treatment for 72h significantly inhibited the proliferation of HCC827, H1650, and HCC827 erlotinib-resistant (HCC827ER) cells with IC50 values of 1.510, 1.328, and 0.909μM, respectively[4]. Treatment of HepG2 cells with 3μM Gambogenic acid for 24h promoted apoptosis, accompanied by a decrease in Bcl-2 levels and an increase in Bax expression levels[5]. Treatment with 1μM Gambogenic acid for 48h inhibited the invasion and migration of A375 cells and induced ferroptosis in A375 cells treated with TGF-β1 (5ng/ml; 48h)[6].
In vivo, Gambogenic acid treatment via intraperitoneally injection at a dose of 2mg/kg/day for 21 days significantly reduced tumor volume and weight in HCT116 cell-xenograft mice, without affecting body weight[7]. Intraperitoneal injection of Gambogenic acid (10mg/kg/day) for 7 consecutive days in male Sprague-Dawley rats can prevent liver oxidative damage caused by acetaminophen (APAP) and alleviate liver histopathological changes caused by APAP[8].
References:
[1] Liu C, Xu J, Guo C, et al. Gambogenic acid induces endoplasmic reticulum stress in colorectal cancer via the aurora a pathway[J]. Frontiers in Cell and Developmental Biology, 2021, 9: 736350.
[2] Zhao Q, Zhong J, Bi Y, et al. Gambogenic acid induces Noxa-mediated apoptosis in colorectal cancer through ROS-dependent activation of IRE1α/JNK[J]. Phytomedicine, 2020, 78: 153306.
[3] Mi L, Xing Z, Zhang Y, et al. Unveiling gambogenic acid as a promising antitumor compound: a review[J]. Planta Medica, 2024, 90(05): 353-367.
[4] Xu L, Meng X, Xu N, et al. Gambogenic acid inhibits fibroblast growth factor receptor signaling pathway in erlotinib-resistant non-small-cell lung cancer and suppresses patient-derived xenograft growth[J]. Cell death & disease, 2018, 9(3): 262.
[5] Yan F, Wang M, Li J, et al. Gambogenic acid induced mitochondrial-dependent apoptosis and referred to phospho-Erk1/2 and phospho-p38 MAPK in human hepatoma HepG2 cells[J]. Environmental toxicology and pharmacology, 2012, 33(2): 181-190.
[6] Wang M, Li S, Wang Y, et al. Gambogenic acid induces ferroptosis in melanoma cells undergoing epithelial-to-mesenchymal transition[J]. Toxicology and applied pharmacology, 2020, 401: 115110.
[7] Zhao Q, Zhong J, Bi Y, et al. Gambogenic acid induces Noxa-mediated apoptosis in colorectal cancer through ROS-dependent activation of IRE1α/JNK[J]. Phytomedicine, 2020, 78: 153306.
[8] Ding Z, Li Y, Tang Z, et al. Role of gambogenic acid in regulating PI3K/Akt/NF-kβ signaling pathways in rat model of acute hepatotoxicity[J]. Bioscience, Biotechnology, and Biochemistry, 2021, 85(3): 520-527.
Gambogenic acid是藤黄的主要活性成分，能抑制Aurora A激酶，IC50值为1.425μM[1]。Gambogenic acid通过活性氧/IRE1α/c-Jun氨基末端激酶信号通路，引发内质网应激介导的细胞凋亡[2]。Gambogenic acid已被广泛用于抗癌剂抑制不同癌细胞生长[3]。
在体外，Gambogenic acid处理72小时能显著抑制HCC827、H1650及HCC827厄洛替尼耐药细胞（HCC827ER）的增殖，IC50值分别为1.510μM、1.328μM和0.909μM[4]。使用3μM的Gambogenic acid处理HepG2细胞24小时可促进细胞凋亡，同时伴随Bcl-2水平下降和Bax表达水平升高[5]。用1μM的Gambogenic acid处理48小时能抑制A375细胞的侵袭和迁移，并在TGF-β1处理的A375细胞中诱导铁死亡[6]。
在体内，通过每日腹腔注射2mg/kg剂量的Gambogenic acid，连续21天治疗，能显著降低HCT116细胞移植瘤小鼠的肿瘤体积和重量，且不影响小鼠体重[7]。在雄性Sprague-Dawley大鼠中连续7天腹腔注射Gambogenic acid，可预防acetaminophen (APAP)引起的肝脏氧化损伤，并减轻APAP导致的肝脏组织病理学变化[8]。