Gossypol

Yellow, crystalline pigment

Exists in 3 tautomeric forms. Yellow crystals from ether

Very soluble in methanol, ethanol, cold dioxane, diethylene glucol, ether, ethyl acetate, acetone, carbon tetrachloride, pyridine, chloroform, DMF, lipds. Freely soluble (with slow desomposition) in dilute aqueous solutions of ammonia and sodium carbonate. Slightly soluble in glycerol, cyclohexane. Insoluble in water.

Insoluble in water; soluble in alcohol

184 °C (from ether); 199 °C (from chloroform); 214 °C (from ligroin)

178 - 183 °C

Bright yellow crystals from acetone, mp 181-184 °C (decomposes). Specific optical rotation: -386 deg to -390 deg at 29 °C/D (concentration = 0.5 g/100g solution in CHCL3) /Gossyol R-Form/

Bright yellow crystals from acetone, mp 181-184 °C (decomposes). Specific optical rotation: +386 deg to +390 deg at 29 °C/D (concentration = 0.5 g/100g solution in CHCL3), uv max (ethanol): 237.5, 277, 378 (log epsilon 4.8, 4.4, 4.2) /Gossyol S-Form/

Danger

H302 (20.5%): Harmful if swallowed [Warning Acute toxicity, oral]；H351 (98.8%): Suspected of causing cancer [Warning Carcinogenicity]；H360 (19.3%): May damage fertility or the unborn child [Danger Reproductive toxicity]

P203, P264, P270, P280, P301+P317, P318, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 83 reports by companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

Regulation (EC) No 178/2002 (amended)

Gossypol: Does not have an individual approval but may be used under an appropriate group standard

0 - Materials that, under emergency conditions, would offer no hazard beyond that of ordinary combustible materials.

0 - Materials that will not burn under typical fire conditions, including intrinsically noncombustible materials such as concrete, stone, and sand.

0 - Materials that in themselves are normally stable, even under fire conditions.

...This study ... aimed to investigate the potential relationship between gossypol-induced cytotoxicity of human promyelocytic leukemia cell line (HL-60) leukemic cells and intracellular serine/threonine protein phosphatase (PP) dynamics and human telomerase reverse transcriptase (hTERT) activity. Gossypol was found to be cytotoxic in HL-60 cells with the IC(50) dose of 4.5 microM. The combination of gossypol and okadaic acid in IC(50) doses revealed the increased cytotoxicity in a time-dependent manner. Treatment of cells with gossypol has shown significant decrease in PP2A activity. The expression of the PP2A catalytic subunit was downregulated in gossypol-treated cells with 24 hours' intervals. hTERT mRNA levels were gradually decreased. In conclusion, during gossypol-induced cytotoxicity, intracellular activity and expression of PP2A was decreased as well as the activity of hTERT. The variation of hTERT activity in gossypol-treated HL-60 cells may be the potential reason for the phosphatase interaction during the gossypol treatment of leukemic cells resulting in cellular cytotoxicity.

Gossypol, a cottonseed extract derivative, acts as a BH3-mimetic, binding to the BH3 pocket of antiapoptotic proteins and displacing pro-death partners to induce apoptosis. ... Since chronic lymphocytic leukemia (CLL) cells express high levels of antiapoptotic proteins that act as a survival mechanism for these replicationally quiescent lymphocytes, we investigated whether gossypol induces apoptosis in these cells and what mechanism underlies gossypol-mediated cytotoxicity. Gossypol induced cell death in a concentration- and time-dependent manner; 24-hour incubation with 30 uM gossypol resulted in 50% cell death (median; range, 10%-80%; n = 47) that was not abrogated by pan-specific caspase inhibitor. Starting at 4 hours, the mitochondrial outer membrane was significantly permeabilized (median, 77%; range, 54%-93%; n = 15). Mitochondrial outer membrane permeabiliztaion (MOMP) was concurrent with increased production of reactive oxygen species (ROS); however, antioxidants did not abrogate gossypol-induced cell death. Mitochondrial membrane permeabilization was also associated with loss of intracellular adenosine triphosphate (ATP), activation of BAX, and release of cytochrome c and apoptosis-inducing factor (AIF), which was translocated to the nucleus. Blocking AIF translocation resulted in a decreased apoptosis, suggesting that AIF contributes to gossypol-mediated cytotoxicity in CLL lymphocytes.

Gossypol, a natural compound present in cottonseeds, displays antiproliferative and pro-apoptotic effects against various cancer cells. The (-)-gossypol enantiomer is a more potent inhibitor of cancer cell growth. Here, the molecular mechanisms of apoptosis induced by (-)-gossypol were studied in human prostate cancer cells. MATERIALS AND METHODS: After the prostate cancer cell DU-145 had been treated with (-)-gossypol, the trypan blue exclusion assay and DNA fragment end-labeling assay were used to stain the dead cells and to detect DNA laddering, respectively. The effects of (-)-gossypol on the expression of apoptotic-regulated gene markers in both death receptor- and mitochondria-mediated apoptotic pathways, such as the Bcl-2 family and caspase, etc., were detected by RT-PCR and Western blot analysis. To further investigate the apoptotic pathways induced by (-)-gossypol, different caspase inhibitors were used to block caspase activities and cell viability was detected by the CellTiter 96 AQueous assay in DU-145 cells. RESULTS: At a 5-10 microM dose-level, (-)-gossypol significantly enhanced apoptosis measured by DNA fragmentation. (-)-Gossypol caused apoptosis in DU-145 cells through the down-regulation of Bcl-2 and Bcl-xL and the up-regulation of Bax at the mRNA and protein levels. (-)-Gossypol also activated caspases-3, -8 and -9 and increased PARP [poly (ADP-ribose) polymerase] cleavage. Furthermore, (-)-gossypol-induced apoptosis might be due to an increase in CAD (caspase-activated deoxyribonuclease) proteins and a decrease in ICAD (inhibitor of CAD) proteins. By using caspase inhibitors, (-)-gossypol caused apoptosis via the caspase-dependent pathways. CONCLUSION: /These/ results indicated that the apoptotic processes caused by (-)-gossypol are mediated by the regulation of the Bcl-2 and caspase families in human prostate cancer cells. /The/ data also suggested that (-)-gossypol may have chemotheraputic benefits for prostate cancer patients.