gambogic-acid has been researched along with Leukemia* in 4 studies
4 other study(ies) available for gambogic-acid and Leukemia
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Anticancer Effect and Apoptosis Induction of Gambogic Acid in Human Leukemia Cell Line K562 In Vitro.
The aim of this study was to investigate the anticancer effect and related mechanisms of gambogic acid (GA), a traditional Chinese medicine, on human leukemia cell line K562, together with the effect on bone marrow mononuclear cells (MNCs).. K562 cells and MNCs were treated with various concentrations and treatment times of GA. Inhibitory rate was detected by use of the Cell Counting Kit-8 (CCK-8) assay. Apoptosis was analyzed by morphological detection, Annexin-V/PI doubling staining, and TUNEL assays. The expression changes of pivotal proteins were evaluated by Western blotting.. GA not only suppressed cell proliferation, but also induced apoptosis of K562 cells in a dose-dependent manner. While it did not significantly inhibit cell proliferation of MNCs, it did induce apoptosis in a dose-dependent manner. CCK-8 assay revealed that the proliferation of K562 cells was significantly inhibited when the concentration of GA was more than 0.5 μM. Morphological detection showed the nuclei became denser and more intense orange in K562 cells after GA treatment compared with the untreated group. The expression levels of BCL-2, nuclear factor-κB (NF-κB), c-myc, phosphatidylinositol3-kinase (PI3K), and phosphorylation of serine-threonine kinase (p-AKT) were down-regulated by GA.. GA significantly suppressed the proliferation of K562 cells, but has less effect on MNCs. The inhibition of K562 cells proliferation and apoptosis induced by GA might be related to the down-regulation of BCL-2, NF-κB, c-myc, PI3K, and p-AKT. Topics: Annexin A5; Antineoplastic Agents; Apoptosis; Blotting, Western; Cell Count; Cell Proliferation; Gene Expression Regulation, Neoplastic; Humans; In Situ Nick-End Labeling; In Vitro Techniques; K562 Cells; Leukemia; NF-kappa B; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-myc; Xanthones | 2015 |
[Effects of Garcinia Acid Combined with Daunorubicin on Expression of Pregnane X Receptor in Leukemia Cell Line K562/A02].
To explore the expression of PXR (Pregnane X receptor) in several malignant hematological cell lines, and to investigate the reversal effect of Gambogic acid (GA) on multi-drug resistance (MDR) of K562/A02 cell line and its reversal mechanism.. Transcription of PXR was detected by real-time PCR in several malignant hematological cell lines. The growth inhibition rate of K562/A02 in different experimental groups was assayed by MTT method, and the expression of PXR protein was measured by Western blot.. PXR gene transcription could be detected in several hematological malignancy cell lines, and it was significantly higher in K562/A02 cell line, compared with the other cell lines used in this experiment. Low-dose GA could enhance cell growth inhibition rate, increasing the effect of chemotherapy, which may be associated with down-regulation of PXR expression. PXR gene transcription and protein expression in GA and DNR+GA groups decreased as compared with control group and the DNR group, suggesting that low-dose GA can down-regulate PXR gene transcription and protein expression.. PXR gene transcription can be detected in several hematological malignancy cell line, which is significantly higher in K562/A02 cell line, as compared with the other cell lines used in this experiment. Low-dose GA can enhance cell growth inhibition rate, increasing the effect of chemotherapy, which may be associated with down-regulation of PXR expression. Topics: Citrates; Daunorubicin; Down-Regulation; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; K562 Cells; Leukemia; Pregnane X Receptor; Real-Time Polymerase Chain Reaction; Receptors, Steroid; Xanthones | 2015 |
Gambogic acid is a tissue-specific proteasome inhibitor in vitro and in vivo.
Gambogic acid (GA) is a natural compound derived from Chinese herbs that has been approved by the Chinese Food and Drug Administration for clinical trials in cancer patients; however, its molecular targets have not been thoroughly studied. Here, we report that GA inhibits tumor proteasome activity, with potency comparable to bortezomib but much less toxicity. First, GA acts as a prodrug and only gains proteasome-inhibitory function after being metabolized by intracellular CYP2E1. Second, GA-induced proteasome inhibition is a prerequisite for its cytotoxicity and anticancer effect without off-targets. Finally, because expression of the CYP2E1 gene is very high in tumor tissues but low in many normal tissues, GA could therefore produce tissue-specific proteasome inhibition and tumor-specific toxicity, with clinical significance for designing novel strategies for cancer treatment. Topics: Animals; Caspases; Cell Death; Cell Proliferation; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP2E1; Drug Screening Assays, Antitumor; Endoplasmic Reticulum Stress; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Silencing; Hep G2 Cells; Humans; K562 Cells; Leukemia; Lymphocytes; Mice; Molecular Docking Simulation; Organ Specificity; Proteasome Endopeptidase Complex; Proteasome Inhibitors; RNA, Small Interfering; Survival Analysis; Trypsin; Ubiquitination; Xanthones | 2013 |
Cluvenone induces apoptosis via a direct target in mitochondria: a possible mechanism to circumvent chemo-resistance?
The synthetic caged Garcinia xanthone, cluvenone, has potent and selective cytotoxicity against numerous cancer cell lines including those that are multi-drug resistant. The direct target of this structurally and functionally unique agent is unknown and that of the parent natural product, gambogic acid (GA), presently in clinical trials, is not yet entirely clear. For the first time, using fluorescently labeled GA (GA-Bodipy), we determined that GA-Bodipy localized in mitochondria and was effectively displaced by cluvenone in competition experiments indicating that the direct target of cluvenone resided in mitochondria and was shared by GA. In agreement with these findings, treatment of HeLa cells with cluvenone or GA resulted in disruption of mitochondrial morphology within 4 h. Furthermore, experiments using the potential sensitive JC-1 dye demonstrated that cells treated with 1 μM cluvenone for 1 h had significant loss of MMP compared to control cells. Examination of Cyt c levels in leukemia cells treated with 1 μM cluvenone resulted in a 4-fold increase in levels of both cytosolic and mitochondrial Cyt c. In agreement with Cyt c release, caspase 9 activity was increased 2.6-fold after treatment of cells for 5 h with 1 μM cluvenone. Remarkably, the caspase-9 inhibitor, Z-LEHD-FMK, blocked cluvenone-induced apoptosis in a dose-dependent manner with apoptosis being completely blocked by 10 μM of the inhibitor. In conclusion, cluvenone, an agent with potent cytotoxicity against multi-drug resistant tumor cells, has direct targets in mitochondria thus setting precedence for drug discovery efforts against these targets in the treatment of refractory cancers. Topics: Apoptosis; Caspase 9; Cell Line, Tumor; Cytochromes c; Drug Resistance, Neoplasm; HeLa Cells; Humans; Leukemia; Mitochondria; Xanthones | 2012 |