Gambogic Acid (Synonyms: GA, β-Guttiferin)

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.