Cancer:
Leukemia, metastatic breast, osteocarcinoma, glioblastoma, breast, lung, liver
Action: Anti-cancer, tumor apoptosis
Gambogic acid (GA) is the principal active ingredient of gamboges which is the resin from various Garcinia species including Garcinia hanburyi (Hook. F.) and Garcinia morella (Panthong et al., 2007). GA is a natural product with potent apoptotic activity. GA has various biological effects, such as anti-inflammatory, analgesic and anti-pyretic as well as anti-cancer activities.
Tumor Apoptosis, Osteocarcinoma, Glioblastoma, Breast, Lung, Liver
GA binding to Transferrin receptor (TfR) induces a unique signal leading to rapid apoptosis of tumor cells. (Kasibhatla et al., 2005; Gu et al., 2008). GA enhances p53 protein level through inhibition of mdm2 oncogene expression and thereby hampers p53 harboring tumor growth. GA could increase the chemotherapeutic effect of cisplatin in human osteosarcoma treatment through inducing the cell-cycle arrest and promoting cell apoptosis (Zhao et al., 2013).
In vitro and in vivo studies have demonstrated its potential as an excellent cytotoxicity against a variety of malignant tumors, including glioblastoma, as well as cancers of the breast, lung and liver. GA is currently investigated in clinical trials in China (Qi et al., 2008).
Leukemia
Gambogic acid (GA) has been found to inhibit the proliferation of Jurkat leukemia cells with 50% inhibitory concentration values of 1.51±0.09 (24 hours), 0.98±0.13 (48 hours), and 0.67±0.12 µmol/L (72 hours). GA was able to induce apoptosis of Jurkat cells. Treated by GA, the expression of DIO-1 was up-regulated, and that of Bcl-2 and NF-κB was down-regulated, leading to the activation of pro-caspase 3. GA induced the translocation of DIO-1 to the nucleus. GA suppressed the proliferation of Jurkat cells by apoptosis induction. DIO-1 triggered early-stage cell death in GA-treated Jurkat cells (Wang et al., 2008).
Metastatic Cancer
Patients with advanced or metastatic cancer who had not received any effective routine conventional treatment, or who had failed to respond to the existing conventional treatment, were randomly assigned to receive either 45 mg/m(2) gambogic acid intravenously from days 1– 5 of a 2-week cycle (Group A), or 45 mg/m(2) every other day for a total of 5 times during a 2-week cycle (Group B). The ORRs were 14.3% in Group A and 0% in Group B. It was not possible to analyze the significant difference because one of the values was zero. The disease control rates (DCRs) were 76.2% in Group A and 61.5% in Group B (P = 0.0456). The observed adverse reactions were mostly Grades I and II, and occurred in most patients after administration of the trial drug. There was no significant difference in the incidence of adverse reactions between the two arms.
The preliminary results of this phase IIa exploratory study suggest that gambogic acid has a favorable safety profile when administered at 45 mg/m(2). The DCR was greater in patients receiving gambogic acid on days 1–5 of a 2-week cycle, but the incidence of adverse reactions was similar irrespective of the administration schedule (Chi et al., 2013).
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