GAMBOGIC ACID Property

Melting point:

88.5°C

Boiling point:

586.06°C (rough estimate)

alpha 

D20 -685° (methanol)

Density 

1.1057 (rough estimate)

refractive index 

1.5290 (estimate)

storage temp. 

-20°C

solubility 

DMSO: ≥10mg/mL

form 

powder

pka

4.58±0.36(Predicted)

color 

yellow to orange

Stability:

Stable for 1 year as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 1 month.

InChIKey

GEZHEQNLKAOMCA-XKZIYDEJSA-N

LogP

6.490 (est)

Safety

Hazard Codes 

T

Risk Statements 

25-36/37/38

Safety Statements 

26-45

RIDADR 

UN 2811 6.1 / PGIII

WGK Germany 

1

RTECS 

PB9268200

HS Code 

29189900

Toxicity

LD50 unreported in mammal (species unspecified): 55mg/kg

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H301Toxic if swalloed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P301+P310IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

GAMBOGIC ACID Chemical Properties,Usage,Production

Description

Gambogic acid (2752-65-0) induces apoptosis in a variety of cell lines acting as an antagonist of Bcl-2 family proteins (IC50 < 1 mM)1, however additional targets may contribute to its cytotoxicity. It suppresses cancer invasion and migration by inhibiting TGFb1-induced epithelial-to-mesenchymal transition.2 Potentiates the chemosensitivity of cancer cells to other agents.3 Down-regulates surviving, reversing docetaxel resistance in cancer cells.4

Uses

antiinflammatory, cytotoxic, inhibits HeLa cells in vitro;

Definition

ChEBI: A natural product found in Garcinia hanburyi.

General Description

This substance is a primary reference substance with assigned absolute purity (considering chromatographic purity, water, residual solvents, inorganic impurities). The exact value can be found on the certificate. Produced by PhytoLab GmbH & Co. KG

Biological Activity

Natural product isolated from the Garcinia hanburyi tree. Induces apoptosis in several tumor cell lines including T47D cells. Activates caspases with an EC 50 value of 0.78-1.64 μ M and competitively inhibits antiapoptotic Bcl-2 family proteins (IC 50 values are 1.47, 1.21, 2.02, 0.66, 1.06 and 0.79 μ M for Bcl-XL, Bcl-2, Bcl-W, Bcl-B, Bfl-1 and Mcl-1 respectively). Also blocks K IR 2.1 channels (EC 50 ≤ 100 nM).

Biochem/physiol Actions

Gambogic acid acts as a caspase activator and apoptosis inducer, which causes an irreversible arrest in the G2/M phase of the cell cycle.

Anticancer Research

Gambogic acid is a xanthonoid, also known as kokum that is a resin from Garciniaindica, that can inhibit the proliferation of human breast, hepatoma, lung, and gastriccarcinoma cells. It is also an apoptotic inducer and inhibits telomerase and theexpression of telomerase reverse transcriptase mRNA and its promoter. It also suppressesCDK7-mediated CDC2/p34 phosphorylation, downregulates Bcl-2, andinteracts with c-myc. By interacting with transferrin receptors, it mediates apoptosisof cancer cells. It inhibits NF-κB pathway. In vivo and in vitro experiments determinedits potential to inhibit angiogenesis and VGEF-2 receptor, and thus it inhibitshuman endothelial cell growth, invasion, and migration, microvessel growth, andtube formation (Zhang et al. 2004; Pandey et al. 2007; Aggarwal et al. 2008).
GA, extract from Garcinia hanburyi, the most important active constituent of gamboge,inhibits the heat shock protein (Hsp90) (Zhang 2010). Hsp90 is the majorprotein in tumour regeneration as well as cell signalling, and its inhibition results ininduction of ER stress, thereby activating UPR target genes and ER stress sensorswhich further cause cell death (Lamoureux et al. 2014). Severe or sustained ERstress increases CHOP expression and stimulates IRE1α apoptotic signalling, ATF6and PERK. CHOP being the major regulator of Bcl2, Bim and DR5 leads to cellularapoptosis preventing tumour progression (Krajarng et al. 2015).

References

1) Zhai et al. (2008), Gambogic acid is an antagonist of antiapoptotic Bcl-2 family proteins; Mol. Cancer Ther. 7 1639 2) Zhao et al. (2017), Gambogic acid suppresses cancer invasion and migration by inhibiting TGFβ1-induced epithelial-to-mesenchymal transition; Oncotarget 8 27120 3) Wei et al. (2017), Gambogic acid potentiates the chemosensitivity of colorectal cancer cells to 5-fluorouracil by inhibiting proliferation and inducing apoptosis; Exp. Ther. Med. 13 662 4) Wang et al. (2008), Gambogic acid, a potent inhibitor of surviving, reverses docetaxel resistance in gastric cancer cells; Cancer Lett. 262 214