Combination Of Gambogic Acid Research Articles

Gambogic acid and chloroquine synergistically induce cell death via increasing mitochondria damage in human NSCLC cells

AbstractGambogic acid is a natural bioactive compound from the brownish resin of the Garcinia hanburyi trees, which has been shown to induce cell death of cancer cells with a synergistic effect together with other compounds. In the present study, we aim to investigate whether the combination of gambogic and chloroquine, one of the inhibitor of autophagy, could increase cell death in human NSCLC cells. As a result, gambogic acid and chloroquine synergistically suppress the growth of NSCLC cells (CI <0.9). Moreover, the combination of gambogic acid and chloroquine significantly promotes apoptosis than that either alone does. Mechanistically, the results demonstrate that gambogic acid increases PINK1 expression at mRNA and protein level, accompanied with downregulation of Tom20, suggesting the mitophagy process is activated. Both silencing PINK1 and treatment of chloroquine could inhibit mitophagy, therefore disrupting the clearance of damaged mitochondria. Thus, co‐treatment of gambogic acid and chloroquine results in an elevated level of ROS, which facilitates cell death. Taken together, our finding highlights that the synergistically inhibitory effect of gambogic acid and chloroquine on NSCLC cells is associated with the accumulation of mitochondrial damage.

Gambogic Acid and Piperine Synergistically Induce Apoptosis in Human Cholangiocarcinoma Cell via Caspase and Mitochondria-Mediated Pathway.

Most cholangiocarcinoma (CCA) patients undergo chemotherapy as a therapeutic approach due to the disease's frequently late diagnosis. However, because CCA is resistant to currently available treatments, the prognosis for this cancer is still quite poor. Combination therapy has emerged as a novel and promising strategy in cancer treatment, as monotherapy frequently results in tumor recurrence and drug resistance. Gambogic acid has been shown to have a synergism with other compounds in combating certain cancer cells. Moreover, piperine has been shown to improve the efficacy of numerous chemotherapy drugs and other anticancer natural substances. However, no research has been done on the combination of these two compounds in the treatment of bile duct cancer. In this study, the cytotoxic activity was determined by using the MTT assay, and then, the combined effect was assessed by using the combination index (CI). We found that the combination of gambogic acid and piperine inhibited cell viability more effectively than either treatment alone, and it also demonstrated a synergistically cytotoxic effect against CCA cells. Interestingly, the findings allowed the use of lower concentrations of gambogic acid in cancer treatment when combined with piperine, which could reduce its adverse effect on normal cholangiocytes. Furthermore, the combination of the two compounds increased CCA cell death by inducing apoptosis via both the extrinsic and intrinsic or mitochondria-mediated pathways, as determined by caspase-3, -8, and -9 activity and the reduction of mitochondrial transmembrane potential (ΔΨm). It is possible that the use of these two natural compounds together could be a promising strategy for the treatment of bile duct cancer.

Combination of gambogic acid with cisplatin enhances the antitumor effects on cisplatin-resistant lung cancer cells by downregulating MRP2 and LRP expression.

Cisplatin resistance is a main clinical problem of lung cancer therapy. Gambogic acid (GA) could prohibit the proliferation of a variety of human cancer cells. However, the effects of GA on cisplatin-resistant lung cancer are still unclear. The objective of the present study was to find out the antitumor effects of GA on cisplatin-resistant human lung cancer A549/DDP cells and further explore its underlying mechanisms. Cell Counting Kit-8 assay was used to observe the impacts of GA and/or cisplatin on the proliferation of lung cancer cells; flow cytometry was used to detect the effects of GA on cell cycle and apoptosis; Western blot was used to examine the effects of GA on the expression of lung resistance protein (LRP) and multidrug resistance-associated protein 2 (MRP2) protein in A549/DDP cells. Our results showed that GA dose- and time-dependently prohibited the proliferation and induced significant cell apoptosis in A549 and A549/DDP cells. GA also induced G0/G1 arrest in both A549/DDP and A549 cells. Moreover, GA upregulated protein expression level of cleaved caspase-3 and Bax and downregulated protein expression level of pro-caspase-9 and Bcl-2 in time- and dose-dependent way in A549/DDP cells. GA combined with cisplatin enhanced the cells apoptotic rate and reduced the cisplatin resistance index in A549/DDP cells. In addition, GA reduced the MRP2 and LRP protein expression level in A549/DDP cells. GA inhibits the proliferation, induces cell cycle arrest and apoptosis in A549/DDP cells. Combination of GA with cisplatin enhances the antitumor effects on cisplatin-resistant lung cancer cells by downregulating MRP2 and LRP expression.

Gambogic Acid Sensitizes Ovarian Cancer Cells to Doxorubicin Through ROS-Mediated Apoptosis

Ovarian cancer is one human malignancy which has response portly to doxorubicin. The anti-cancer activity of gambogic acid has been tested in in vitro and in vivo studies. In this study, we showed that gambogic acid, a natural compound, could potentiate the anticancer activity of doxorubicin in ovarian cancer through ROS-mediated apoptosis. Platinum-resistant human ovarian cancer cell line (SKOV-3) was treated with gambogic acid, doxorubicin, or the combination of both to investigate cell proliferation and apoptosis. We found that the combination of gambogic acid and doxorubicin causes synergistic loss of cell viability in SKOV-3 cells and this synergistic effect correlated with increased cellular ROS accumulation. Moreover, in vivo results showed that gambogic acid and doxorubicin combination resulted in a synergistic suppressing effect on tumor growth in ovarian cancer mice model. Taken together, the results suggested that doxorubicin in combination with gambogic acid might provide a promising therapeutic strategy to enhance chemosensitivity of ovarian cancer to doxorubicin.