Natural Product (NP) Details

General Information of the NP (ID: NP5023)
Name
Gambogic acid
Synonyms
(-)-Gambogic Acid; Gambogic-acid; UNII-8N585K83U2; beta-Guttiferin; Cambogic acid; B''-Guttiferin; 8N585K83U2; Guttic acid; (Z)-4-((1S,3aR,5S,11R,14aS)-8-hydroxy-2,2,11-trimethyl-13-(3-methylbut-2-en-1-yl)-11-(4-methylpent-3-en-1-yl)-4,7-dioxo-2,3a,4,5,7,11-hexahydro-1H-1,5-methanofuro[3,2-g]pyrano[3,2-b]xanthen-3a-yl)-2-methylbut-2-enoic acid; CHEBI:67521; R-gambogic acid; Gambogic acid;; alpha-Gambogic acid; C38H44O8; Gambogic acid(R+S);; CHEMBL555017; 3-Iodo-5-nitro (1H)indazole; SCHEMBL16160279; BCP21539; HY-N0087; ZINC3933041; BDBM50366237; MFCD16878985; s2448; CCG-270284; CS-1456; BP-22199; Gambogic acid, >=95% (HPLC), powder; AB0029018; G-250; X1145; Q5519727; (2Z)-2-Methyl-4-[(1R,3aS,5S,11R,14aS)-3a,4,5,7-tetrahydro-8-hydroxy-3,3,11-trimethyl-13-(3-methyl-2-butenyl)-11-(4-methyl-3-pentenyl)-7,15-dioxo-1,5-methano-1H,3H,11H-furo[3,4-g]pyrano[3,2-b]xanthen-1-yl]-2-butenoic acid.; 1,5-Methano-1H,3H,11H-furo(3,4-g)pyrano(3,2-b)xanthene-1-crotonic acid, 3a,4,5,7-tetrahydro-8-hydroxy-alpha,3,3,11-tetramethyl-13-(3-methyl-2-butenyl)-11-(4-methyl-3-pentenyl)-7,15-dioxo-, (Z)-
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Species Origin Garcinia hanburyi ...     Click to Show/Hide
Garcinia hanburyi
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Malpighiales
Family: Clusiaceae
Genus: Garcinia
Species: Garcinia hanburyi
Garcinia morella
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Malpighiales
Family: Clusiaceae
Genus: Garcinia
Species: Garcinia morella
Disease Lung cancer [ICD-11: 2C25] Investigative [1]
Structure
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2D MOL

3D MOL

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Formula
C38H44O8
PubChem CID
9852185
Canonical SMILES
CC(=CCCC1(C=CC2=C(C3=C(C(=C2O1)CC=C(C)C)OC45C6CC(C=C4C3=O)C(=O)C5(OC6(C)C)CC=C(C)C(=O)O)O)C)C
InChI
1S/C38H44O8/c1-20(2)10-9-15-36(8)16-14-24-29(39)28-30(40)26-18-23-19-27-35(6,7)46-37(33(23)41,17-13-22(5)34(42)43)38(26,27)45-32(28)25(31(24)44-36)12-11-21(3)4/h10-11,13-14,16,18,23,27,39H,9,12,15,17,19H2,1-8H3,(H,42,43)/b22-13-/t23-,27+,36-,37+,38-/m1/s1
InChIKey
GEZHEQNLKAOMCA-RRZNCOCZSA-N
CAS Number
CAS 2752-65-0
Herb ID
HBIN027097
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Cisplatin      Bladder cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BIRC5  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP8  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
Down-regulation Expression ERK2  Molecule Info 
Pathway MAP
Up-regulation Expression FAS  Molecule Info 
Pathway MAP
Down-regulation Expression HMOX1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation JNK1  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
Up-regulation Expression p105  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation p38 beta  Molecule Info 
Pathway MAP
Up-regulation Expression RELA  Molecule Info 
Pathway MAP
Down-regulation Expression XIAP  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
NCI-H460 CVCL_0459 Lung large cell carcinoma Homo sapiens
NCI-H1299 CVCL_0060 Lung large cell carcinoma Homo sapiens
                    In-vivo Model To determine the in vivo antitumour activity of GA combined with CDDP, viable A549 cells (5 * 106/100ul PBS per mouse) were subcutaneously injected into the right flank of 7- to 8-week-old male SCID mice.
                    Experimental
                    Result(s)		 Gambogic acid synergistically potentiates cisplatin-induced apoptosis in non-small-cell lung cancer through suppressing NF-KappaB and MAPK/HO-1 signalling.
          MG132      Lung cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
H22 CVCL_H613 Hepatocellular carcinoma of the mouse Mus musculus
                    In-vivo Model Murine hepatoma H22 cells (10 * 106) suspended in 0.2 ml of serum-free RPMI 1640 were inoculated s.c. in the left armpit of each mouse.
                    Experimental
                    Result(s)		 The combination of natural product gambogic acid and the proteasome inhibitor MG132 or MG262 results in a synergistic inhibitory effect on growth of malignant cells and tumors in allograft animal models and there was no apparent systemic toxicity observed in the animals treated with the combination.
          TNF-related apoptosis inducing ligand      Lung cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-xL  Molecule Info 
Pathway MAP
Down-regulation Expression BID  Molecule Info 
Pathway MAP
Up-regulation Expression BID  Molecule Info 
Pathway MAP
Down-regulation Expression BIRC5  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP7  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP8  Molecule Info 
Pathway MAP
Down-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Up-regulation Expression XIAP  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Up-regulation Cytochrome c release
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Gambogic acid sensitizes breast cancer cells to TRAIL-induced apoptosis by promoting the crosstalk of extrinsic and intrinsic apoptotic signalings.
          Chloroquine      Malaria     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BECN1  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
Up-regulation Expression MAP1LC3A  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression SQSTM1  Molecule Info 
Pathway MAP
                    In-vitro Model PANC-1 CVCL_0480 Pancreatic ductal adenocarcinoma Homo sapiens
BxPC-3 CVCL_0186 Pancreatic ductal adenocarcinoma Homo sapiens
                    In-vivo Model Xenograft tumor models were created by subcutaneously injecting 5*106 BxPC-3 cells into the right flank of the mice.
                    Experimental
                    Result(s)		 Gambogic acid induces autophagy and combines synergistically with chloroquine to suppress pancreatic cancer by increasing the accumulation of reactive oxygen species.
          Sunitinib      Malignant digestive organ neoplasm     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Down-regulation Expression VEGFA  Molecule Info 
Pathway MAP
                    In-vitro Model 786-O CVCL_1051 Renal cell carcinoma Homo sapiens
Caki-1 CVCL_0234 Clear cell renal cell carcinoma Homo sapiens
                    In-vivo Model Caki-1 cells (2x106) in 100 ul RPMI-1640 and 100 ul of matrigel were used to inject subcutaneously into each mouse (5-week-old male athymic BALB/c nu/nu mice).
                    Experimental
                    Result(s)		 The joint use of GA and SU can provide greater antitumor efficacy compared to either drug alone.
          MG262      Ovarian cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
H22 CVCL_H613 Hepatocellular carcinoma of the mouse Mus musculus
                    In-vivo Model Murine hepatoma H22 cells (10 * 106) suspended in 0.2 ml of serum-free RPMI 1640 were inoculated s.c. in the left armpit of each mouse.
                    Experimental
                    Result(s)		 The combination of natural product gambogic acid and the proteasome inhibitor MG132 or MG262 results in a synergistic inhibitory effect on growth of malignant cells and tumors in allograft animal models and there was no apparent systemic toxicity observed in the animals treated with the combination.
          5-fluorouracil      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage PAEP  Molecule Info 
Pathway MAP
Down-regulation Expression PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model BGC-823 CVCL_3360 Gastric cancer Homo sapiens
                    In-vivo Model Forty mice were inoculated sub cutaneously with injections of 1 * 106 BGC-823 cells/mouse.
                    Experimental
                    Result(s)		 GA attenuated 5-FU-induced apoptosis by modulating metabolic enzymes of 5-FU and the antigastric cancer effect of two drugs combination was much stronger than that of GA or 5-FU alone.
          Doxorubicin      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression ABCB1  Molecule Info 
Pathway MAP
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-xL  Molecule Info 
Pathway MAP
Down-regulation Expression BIRC5  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP8  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
Up-regulation Expression FAS  Molecule Info 
Pathway MAP
Down-regulation Expression NFKBIA  Molecule Info 
Pathway MAP
Up-regulation Expression NFKBIA  Molecule Info 
Pathway MAP
Up-regulation Expression p105  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Up-regulation Expression RELA  Molecule Info 
Pathway MAP
Down-regulation Expression XIAP  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
                    In-vivo Model Viable A549 cells (5*106/100 ul PBS per mouse) were mixed with 50% Matrigel, and then subcutaneously injected into the right flank of 7- to 8- week old male Balb/c nude mice.
                    Experimental
                    Result(s)		 Suppression of NF-KappaB signaling and P-glycoprotein function by gambogic acid synergistically potentiates adriamycin -induced apoptosis in lung cancer.
          Gemcitabine      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAK  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression RRM2  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
NCI-H1299 CVCL_0060 Lung large cell carcinoma Homo sapiens
                    In-vivo Model The tumor xenografts were established by injecting 2 * 107 A549 cells per mouse in 100 ul DMEM medium and Matrigel (Corning Inc., Corning, NY) in 1:1 ratio on the dorsal flank of athymic male nude mice (6-8-week-old).
                    Experimental
                    Result(s)		 Gambogic acid potentiates gemcitabine induced anticancer activity in non-small cell lung cancer.
    β. A List of Drug(s) Whose Resistance can be Reversed by This NP
          Gefitinib      Lung cancer     Click to Show/Hide the Molecular Data of This Drug
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [10]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation MEK1  Molecule Info 
Pathway MAP
                    In-vitro Model NCI-H1975 CVCL_1511 Lung adenocarcinoma Homo sapiens
                    In-vivo Model The mice were subcutaneously injected with 1*107 NCI-H1975 cells suspended in 100 uL of Matrigel.
                    Experimental
                    Result(s)		 Gefitinib in combination with GA resulted in antitumor growth in the EGFR-T790M secondary mutation NCI-H1975 tumor model due to an enhanced apoptotic effect.
          Imatinib      Mantle cell lymphoma     Click to Show/Hide the Molecular Data of This Drug
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [11]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation ABL  Molecule Info 
Pathway MAP
Up-regulation Expression AIFM1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation BCR  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP8  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation CRKL  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ERK2  Molecule Info 
Pathway MAP
Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation STAT5B  Molecule Info 
Pathway MAP
Down-regulation Expression XIAP  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Up-regulation Cytochrome c release
                    In-vitro Model KBM-5 CVCL_0373 Chronic myelogenous leukemia Homo sapiens
K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
KBM5-T315I Chronic myeloid leukemia Homo sapiens
                    In-vivo Model A total of 3 * 107 of KBM5 or KBM5-T315I cells were inoculated subcutaneously on the flanks of 5-week-old male nude mice.
                    Experimental
                    Result(s)		 Gambogic acid induces apoptosis in imatinib-resistant chronic myeloid leukemia cells via inducing proteasome inhibition and caspase-dependent Bcr-Abl downregulation.
References
Reference 1 Gambogic Acid Shows Anti-Proliferative Effects on Non-Small Cell Lung Cancer (NSCLC) Cells by Activating Reactive Oxygen Species (ROS)-Induced Endoplasmic Reticulum (ER) Stress-Mediated Apoptosis. Med Sci Monit. 2019 May 29;25:3983-3988.
Reference 2 Gambogic acid synergistically potentiates cisplatin-induced apoptosis in non-small-cell lung cancer through suppressing NF-KappaB and MAPK/HO-1 signalling. Br J Cancer. 2014 Jan 21;110(2):341-52.
Reference 3 Gambogic acid enhances proteasome inhibitor-induced anticancer activity. Cancer Lett. 2011 Feb 28;301(2):221-8.
Reference 4 Gambogic acid sensitizes breast cancer cells to TRAIL-induced apoptosis by promoting the crosstalk of extrinsic and intrinsic apoptotic signalings. Food Chem Toxicol. 2018 Sep;119:334-341.
Reference 5 Gambogic acid induces autophagy and combines synergistically with chloroquine to suppress pancreatic cancer by increasing the accumulation of reactive oxygen species. Cancer Cell Int. 2019 Jan 5;19:7.
Reference 6 Targeting renal cell carcinoma with gambogic acid in combination with sunitinib in vitro and in vivo. Asian Pac J Cancer Prev. 2012;13(12):6463-8.
Reference 7 Synergistic effect of 5-fluorouracil with gambogic acid on BGC-823 human gastric carcinoma. Toxicology. 2009 Feb 4;256(1-2):135-40.
Reference 8 Suppression of NF-KappaB signaling and P-glycoprotein function by gambogic acid synergistically potentiates adriamycin -induced apoptosis in lung cancer. Curr Cancer Drug Targets. 2014;14(1):91-103.
Reference 9 Gambogic acid potentiates gemcitabine induced anticancer activity in non-small cell lung cancer. Eur J Pharmacol. 2020 Dec 5;888:173486.
Reference 10 Combined therapy with EGFR TKI and gambogic acid for overcoming resistance in EGFR-T790M mutant lung cancer. Oncol Lett. 2015 Oct;10(4):2063-2066.
Reference 11 Gambogic acid induces apoptosis in imatinib-resistant chronic myeloid leukemia cells via inducing proteasome inhibition and caspase-dependent Bcr-Abl downregulation. Clin Cancer Res. 2014 Jan 1;20(1):151-63.
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