Gambogic Acid A cell-permeable caspase activator and apoptosis inducer commonly used in studies of breast, lung, and liver cancers[1].
Gambogic Acid (1.2-4.8μM; 24-72h) reduced the viability of Jurkat and Molt-4 cells in a dose-dependent manner, The IC50 values of Gambogic Acid for Jurkat and Molt-4 were 2.23 and 3.03µM, respectively[2]. Gambogic Acid (2.4, 4.8µM; 72h) at concentrations of 2.4 and 4.8µM led to a remarkable increase in G2/M phase, with a corresponding decrease in the S phase compared with exposure of cells to 1.2µM Gambogic Acid[3]. Gambogic Acid (1μM; 24h) treatment increased the levels of poly-ubiquitinated proteins, proteasome-substrate proteins (e.g. Nrf1, Mcl-1, and Noxa) and ER stress marker proteins (e.g. phospho-eIF2α, ATF4, and CHOP) [4].
Gambogic Acid (4, 8mg/kg; ip; twice) dose-dependently reduced the tumor size without inducing any loss of body weight[4]. In murine CT26 tumor-bearing mouse models, the treatment with Gambogic Acid (2, 8mg/kg; bid; 12d) reduced the volumes and weights of CRC solid tumors,The average of tumor weight decreased from 1.139g (control group) to 0.445g (low-dose group), or 0.214g (high-dose group) [5].
References:
[1]Vichitsakul K, Laowichuwakonnukul K, Soontornworajit B, et al. Anti-proliferation and induction of mitochondria-mediated apoptosis by Garcinia hanburyi resin in colorectal cancer cells[J]. Heliyon, 2023, 9(6).
[2].Zhai D, Jin C, Shiau CW, Kitada S, Satterthwait AC, Reed JC. Gambogic acid is an antagonist of antiapoptotic Bcl-2 family proteins. Mol Cancer Ther. 2008 Jun;7(6):1639-46.
[3].Gambogic acid inhibits proliferation and induces apoptosis of human acute T‑cell leukemia cells by inducing autophagy and downregulating β‑catenin signaling pathway: Mechanisms underlying the effect of Gambogic acid on T‑ALL cells. Oncol Rep. 2020 Oct;44(4):1747-1757.
[4]. Seo MJ, Lee DM, Kim IY, Lee D, Choi MK, Lee JY, Park SS, Jeong SY, Choi EK, Choi KS. Gambogic acid triggers vacuolization-associated cell death in cancer cells via disruption of thiol proteostasis. Cell Death Dis. 2019 Feb 22;10(3):187.
[5]. Xu H, Zhang D, Wei R, Zhou Y, Dai G, Li J, Sun Y, Li F, Xi L. Gambogic Acid Induces Pyroptosis of Colorectal Cancer Cells through the GSDME-Dependent Pathway and Elicits an Antitumor Immune Response. Cancers (Basel). 2022 Nov 9;14(22):5505.
Gambogic Acid 是一种细胞渗透性 caspase 激活剂和细胞凋亡诱导剂，常用于乳腺癌、肺癌和肝癌等的研究[1]。
Gambogic Acid（1.2-4.8μM；24-72h）以剂量依赖性方式降低 Jurkat 和 Molt-4 细胞的活力，Gambogic Acid对 Jurkat 和 Molt-4 的 IC50 值分别为 2.23 和 3.03µM[2]。浓度为 2.4 和 4.8µM 的Gambogic Acid（2.4，4.8µM；72h）导致 G2/M 期显著增加，而与暴露于 1.2µM Gambogic Acid的细胞相比，S 期相应减少[3]。Gambogic Acid（1μM；24 h）治疗可增加多泛素化蛋白、蛋白酶体底物蛋白 (例如 Nrf1、Mcl-1 和 Noxa) 和 ER 应激标记蛋白 (例如磷酸化 eIF2α、ATF4 和 CHOP) 的水平 [4]。
Gambogic Acid（4，8mg/kg；ip；twice）剂量依赖性地缩小了肿瘤大小，而不会引起体重减轻[4]。在小鼠CT26肿瘤模型中，Gambogic Acid（2.8mg/kg；bid；12d）治疗可减小CRC实体瘤的体积和重量，平均肿瘤重量从1.139g(对照组)降低到0.445g(低剂量组)或0.214g(高剂量组)[5]。