Natural Product (NP) Details

General Information of the NP (ID: NP6128)
Name
Gossypol
Synonyms
(-)-Gossypol; 90141-22-3; (+)-Gossypol; Pogosin; Tash 1; racemic-Gossypol; (R)-(-)-Gossypol; (R)-Gossypol; (+-)-Gossypol; (+/-)-Gossypol; CCRIS 2689; NSC56817; NSC 56817; NSC 624336; BRN 1917878; CHEMBL51483; AI3-22957; 20300-26-9; 1,1',6,6',7,7'-Hexahydroxy-5,5'-diisopropyl-3,3'-dimethyl-[2,2'-binaphthalene]-8,8'-dicarbaldehyde; 2,2'-bi[8-Formyl-1,6,7-trihydroxy-5-isopropyl-3-methylnaphthalene]; 2,2'-Bis(1,6,7-trihydroxy-3-methyl-5-isopropyl-8-aldehydonaphthalene); NSC624336; Gossypol acetate
    Click to Show/Hide
Species Origin Gossypium herbaceum ...     Click to Show/Hide
Gossypium herbaceum
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Malvales
Family: Malvaceae
Genus: Gossypium
Species: Gossypium herbaceum
Disease Prostate cancer [ICD-11: 2C82] Phase 2 [1]
Structure
Click to Download Mol
2D MOL

3D MOL

    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C30H30O8
PubChem CID
3503
Canonical SMILES
CC1=CC2=C(C(=C(C(=C2C(C)C)O)O)C=O)C(=C1C3=C(C4=C(C=C3C)C(=C(C(=C4C=O)O)O)C(C)C)O)O
InChI
1S/C30H30O8/c1-11(2)19-15-7-13(5)21(27(35)23(15)17(9-31)25(33)29(19)37)22-14(6)8-16-20(12(3)4)30(38)26(34)18(10-32)24(16)28(22)36/h7-12,33-38H,1-6H3
InChIKey
QBKSWRVVCFFDOT-UHFFFAOYSA-N
CAS Number
CAS 20300-26-9
Herb ID
HBIN028351
SymMap ID
SMIT15675
TTD Drug ID
D0Z0HH
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          TRAIL/Apo2L      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 [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Activity CASP3  Molecule Info 
Pathway MAP
                    In-vitro Model NCI-H460 CVCL_0459 Lung large cell carcinoma Homo sapiens
NCI-H322 CVCL_1556 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Gossypol profoundly sensitizes thoracic cancer cells to the cytotoxic effect of Apo2L/TRAIL via activation of the mitochondria-dependent death signaling pathway.
          Imatinib      Mantle cell lymphoma     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		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-xL  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Up-regulation Cytochrome c release
                    In-vitro Model K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
                    Experimental
                    Result(s)		 Gossypol and its combination with imatinib induce apoptosis in human chronic myeloid leukemic cells.
          Zoledronic      Mineral excesses     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		 Up-regulation Expression BAD  Molecule Info 
Pathway MAP
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BIRC2  Molecule Info 
Pathway MAP
Down-regulation Expression BIRC3  Molecule Info 
Pathway MAP
Down-regulation Expression BIRC5  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression CDKN1B  Molecule Info 
Pathway MAP
Down-regulation Expression CLSPN  Molecule Info 
Pathway MAP
Up-regulation Expression FAS  Molecule Info 
Pathway MAP
Down-regulation Expression HMOX1  Molecule Info 
Pathway MAP
Down-regulation Expression HSP20  Molecule Info 
Pathway MAP
Down-regulation Expression HSPD1  Molecule Info 
Pathway MAP
Down-regulation Expression ML-IAP  Molecule Info 
Pathway MAP
Down-regulation Expression PON2  Molecule Info 
Pathway MAP
Down-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model DU145 CVCL_0105 Prostate carcinoma Homo sapiens
                    Experimental
                    Result(s)		 GP significantly enhances the anti-tumor activity of ZA in hormone- and drug-resistant prostate cancer cells by targeting many pivotal apoptosis-related proteins.
          BRD4770      Pancreatic 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 [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression MAP1LC3A  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Increase Autophagosome formation
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
HPAC CVCL_3517 Pancreatic adenocarcinoma Homo sapiens
PANC-1 CVCL_0480 Pancreatic ductal adenocarcinoma Homo sapiens
HeLa CVCL_0030 Endocervical adenocarcinoma Homo sapiens
PC-3 CVCL_0035 Prostate carcinoma Homo sapiens
                    Experimental
                    Result(s)		 The combination of gossypol and BRD4770 increased LC3-II levels and the autophagosome number in PANC-1 cells, and the compound combination appears to act in a BNIP3-dependent manner, suggesting that these compounds act together to induce autophagy-related cell death in pancreatic cancer cells.
          5-fluorouracil      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     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		 Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression TYMS  Molecule Info 
Pathway MAP
                    In-vitro Model HT-29 CVCL_0320 Colon adenocarcinoma Homo sapiens
HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
RKO CVCL_0504 Colon carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Gossypol sensitizes the antitumor activity of 5-FU through down-regulation of thymidylate synthase in human colon carcinoma cells.
          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 [7]
                    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
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Increase Cell cycle arrest in S phase
                    In-vitro Model SW982 CVCL_1734 Biphasic synovial sarcoma Homo sapiens
                    Experimental
                    Result(s)		 Combination therapy with L gossypol and low-concentration doxorubicin inhibited cell proliferation and induced apoptosis in SW982 HSSCs at a significantly greater level compared with either treatment alone.
    β. A List of Drug(s) Whose Resistance can be Reversed by This NP
          Gemcitabine      Solid tumour/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 [8]
                    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
Up-regulation Expression PMAIP1  Molecule Info 
Pathway MAP
                    In-vitro Model CNE-1 CVCL_6888 Human nasopharyngeal carcinoma Homo sapiens
CNE-2 CVCL_6889 Human nasopharyngeal carcinoma Homo sapiens
HK-1 CVCL_7047 Lung large cell carcinoma Homo sapiens
AGS CVCL_0139 Gastric adenocarcinoma Homo sapiens
SNU-1 CVCL_0099 Gastric adenocarcinoma Homo sapiens
YCC-16 CVCL_9649 Gastric adenocarcinoma Homo sapiens
SK-BR-3 CVCL_0033 Breast adenocarcinoma Homo sapiens
T-47D CVCL_0553 Invasive breast carcinoma Homo sapiens
MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
HONE Nasopharyngeal carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combination therapy with gossypol reveals synergism against gemcitabine resistance in cancer cells with high BCL-2 expression.
Target and Pathway
Target(s) Apoptosis regulator Bcl-2 (BCL-2)  Molecule Info  [9]
KEGG Pathway NF-kappa B signaling pathway Click to Show/Hide
2 HIF-1 signaling pathway
3 Sphingolipid signaling pathway
4 Protein processing in endoplasmic reticulum
5 PI3K-Akt signaling pathway
6 Apoptosis
7 Adrenergic signaling in cardiomyocytes
8 Focal adhesion
9 Neurotrophin signaling pathway
10 Cholinergic synapse
11 Amyotrophic lateral sclerosis (ALS)
12 Toxoplasmosis
13 Tuberculosis
14 Hepatitis B
15 Epstein-Barr virus infection
16 Pathways in cancer
17 MicroRNAs in cancer
18 Colorectal cancer
19 Prostate cancer
20 Small cell lung cancer
NetPath Pathway IL5 Signaling Pathway Click to Show/Hide
2 TCR Signaling Pathway
3 IL2 Signaling Pathway
4 IL3 Signaling Pathway
5 Leptin Signaling Pathway
6 RANKL Signaling Pathway
7 TSLP Signaling Pathway
Panther Pathway Apoptosis signaling pathway Click to Show/Hide
2 Oxidative stress response
3 CCKR signaling map ST
Pathway Interaction Database Role of Calcineurin-dependent NFAT signaling in lymphocytes Click to Show/Hide
2 IL2-mediated signaling events
3 IL2 signaling events mediated by PI3K
4 Ceramide signaling pathway
5 Direct p53 effectors
6 RXR and RAR heterodimerization with other nuclear receptor
7 ATF-2 transcription factor network
8 C-MYB transcription factor network
9 HIV-1 Nef: Negative effector of Fas and TNF-alpha
10 Caspase Cascade in Apoptosis
11 Signaling events mediated by Stem cell factor receptor (c-Kit)
12 EPO signaling pathway
13 IL2 signaling events mediated by STAT5
14 Validated targets of C-MYC transcriptional repression
Reactome Activation of BAD and translocation to mitochondria Click to Show/Hide
2 BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members
3 The NLRP1 inflammasome
WikiPathways DNA Damage Response (only ATM dependent) Click to Show/Hide
2 Senescence and Autophagy in Cancer
3 IL-2 Signaling Pathway
4 FAS pathway and Stress induction of HSP regulation
5 Focal Adhesion
6 Kit receptor signaling pathway
7 IL-3 Signaling Pathway
8 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
9 Apoptosis
10 Nanoparticle triggered autophagic cell death
11 Amyotrophic lateral sclerosis (ALS)
12 Integrated Pancreatic Cancer Pathway
13 Corticotropin-releasing hormone
14 Interleukin-11 Signaling Pathway
15 Prostate Cancer
16 miR-targeted genes in muscle cell - TarBase
17 miR-targeted genes in lymphocytes - TarBase
18 miR-targeted genes in leukocytes - TarBase
19 Integrated Breast Cancer Pathway
20 Integrated Cancer pathway
21 Intrinsic Pathway for Apoptosis
22 Apoptosis Modulation and Signaling
23 TP53 Network
24 Influenza A virus infection
25 IL-5 Signaling Pathway
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4204).
Reference 2 Gossypol, a phytochemical with BH3-mimetic property, sensitizes cultured thoracic cancer cells to Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand. J Thorac Cardiovasc Surg. 2006 Dec;132(6):1356-62.
Reference 3 (-)Gossypol and its combination with imatinib induce apoptosis in human chronic myeloid leukemic cells. Leuk Lymphoma. 2007 Nov;48(11):2204-12.
Reference 4 Targeting apoptosis in the hormone- and drug-resistant prostate cancer cell line, DU-145, by gossypol/zoledronic acid combination. Cell Biol Int. 2009 Nov;33(11):1165-72.
Reference 5 Gossypol and an HMT G9a inhibitor act in synergy to induce cell death in pancreatic cancer cells. Cell Death Dis. 2013 Jun 27;4(6):e690.
Reference 6 Gossypol sensitizes the antitumor activity of 5-FU through down-regulation of thymidylate synthase in human colon carcinoma cells. Cancer Chemother Pharmacol. 2015 Sep;76(3):575-86.
Reference 7 Combination of L-gossypol and low-concentration doxorubicin induces apoptosis in human synovial sarcoma cells. Mol Med Rep. 2015 Oct;12(4):5924-32.
Reference 8 Combination therapy with gossypol reveals synergism against gemcitabine resistance in cancer cells with high BCL-2 expression. PLoS One. 2012;7(12):e50786.
Reference 9 Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40.
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link