Disease relevance of gossypol

• Lactic dehydrogenase isozymes, 31P magnetic resonance spectroscopy, and in vitro antimitochondrial tumor toxicity with gossypol and rhodamine-123 [1].
• Cytogenetic analysis of a gossypol-induced murine myxosarcoma [2].
• A 1-week pretreatment period followed by daily administration of gossypol in which 30 mg gossypol/kg body weight/day was administered via orogastric tube delayed the onset of visible tumor in the subsequent weeks [3].
• These data suggest that gossypol may provide a beneficial effect in patients with adrenocortical carcinoma [3].
• These results indicate that gossypol has differential cytotoxic effects against certain tumor cell types, such as melanoma and colon carcinoma, and suggest that it might be of potential therapeutic value [4].

High impact information on gossypol

• Cytogenetic analysis of gossypol acetate-induced murine myxosarcoma demonstrated a stemline of 78 chromosomes and the presence of three marker (M) chromosomes produced by robertsonian translocation [2].
• Induction of DNA fragmentation by chelerythrine, calphostin C, and gossypol was biphasic, resulting in a sharp decline in effect at concentrations above 5 microM, 0.1 microM, and 100 microM, respectively, whereas maximal and more stable effects were observed in response to H7 (100 microM) [5].
• The action of gossypol, a polyphenolic bisnaphthalene aldehyde, on a number of drug-sensitive and multidrug-resistant cell lines, in particular MCF-7 WT and MCF-7 ADR cells, was studied and compared to the effects of rhodamine 123 [6].
• The resistance to rhodamine 123 and sensitivity to gossypol was also observed with cells transfected with the MDR1 gene, showing that the difference in toxicity is mainly due to the different response to the P-170 drug efflux pump [6].
• The membranes of viable SW-13 cells exposed to gossypol became more rigid after a 1-day exposure to gossypol, the polarization constant, P, increasing from 0.229 to 0.352 [3].

Chemical compound and disease context of gossypol

• Inhibitors of PKC known to have minimal effects on RNA synthesis, quercetin and gossypol, totally inhibited both the elevations of ODC activity and [3H]thymidine incorporation in response to PRL in Nb 2 lymphoma cells.(ABSTRACT TRUNCATED AT 400 WORDS)[7]
• Derivatives of gossypol, in which the aldehyde functional groups that contribute to toxicity have been modified, retain or even show enhanced biological activity [8].
• Groups of young male rats were subcutaneously injected daily with 0.2 ml gossypol acetic acid in doses of 1, 5, or 10 mg per kg body weight [9].
• Antiproliferative activity of gossypol and gossypolone on human breast cancer cells [10].
• The effect of the association of Gossypol and Lonidamine on the energy metabolism of Ehrlich ascites tumor cells [11].

Biological context of gossypol

• Effect of gossypol on DNA synthesis and cell cycle progression of mammalian cells in vitro [12].
• Gossypol acts noncompetitively, interfering with the binding site for the cyclophilin 18.CsA complex in CaN [13].
• Gossypol induces DNA strand breaks in human fibroblasts and sister chromatid exchanges in human lymphocytes in vitro [14].
• The conjugates do not influence the kinetics of modification of PLA2 by gossypol in the aqueous phase, and the enzyme at the interface is not modified in the presence of the conjugates [15].
• S-100, but not calmodulin, promoted phosphorylation of the 19K Mr protein in a Ca2+-independent manner, and this reaction was inhibited by gossypol [16].

Anatomical context of gossypol

• Differential cytotoxic effect of gossypol on human melanoma, colon carcinoma, and other tissue culture cell lines [4].
• For example, slow growing cells, such as normal embryonic lung fibroblasts and mammary adenocarcinoma, were least sensitive, requiring over 30 microM gossypol in order to kill 90% of cells after 48 hr of treatment [4].
• Gossypol, a yellow pigment from the cotton plant (Gossypium) was found to have anti-tumor cell effects against several tumor cell lines grown in tissue culture [4].
• Gossypol, a hyperthermic sensitizer of HeLa cells [17].
• Incubation of HL-60 cells for 6 h with chelerythrine and calphostin C (highly specific inhibitors that act at the regulatory domain) or H7 and gossypol (nonspecific inhibitors that act at the PKC catalytic domain) produced concentration-dependent increases in DNA fragmentation [5].

Associations of gossypol with other chemical compounds

• In HeLa cells pretreated with gossypol (3.4-17.5 microM) for 8-16 h we observed a dose- and time-dependent decrease (50-75%) in DNA cleavage compared to that quantified in cells treated with m-AMSA alone [18].
• In recent years, two antispermatogenic drugs - gossypol and lonidamine (Fig. I) - have been reported to inhibit the growth of Trypanosoma cruzi in culture [19].
• The remaining anti-aggregatory effect of endothelial cells could be prevented with the EDRF inhibitors, gossypol, haemoglobin and methylene blue [20].
• In cotton (Gossypium hirsutum) the enzyme (+)-delta-cadinene synthase (CDNS) catalyzes the first committed step in the biosynthesis of cadinane-type sesquiterpenes, such as gossypol, that provide constitutive and inducible protection against pests and diseases [21].
• The adenosine triphosphate (ATP) content in spermatids was reduced markedly, although lactate oxidation to CO2 and mitochondrial respiration were stimulated by gossypol [22].
• In vitro, Bcl-2-expressing B cells from transgenic mice were more sensitive to cytotoxicity induced by apogossypol than gossypol, with LD50 values of 3 to 5 microM and 7.5 to 10 microM, respectively [23].

Gene context of gossypol

• Upregulation of Fas/Fas ligand-mediated apoptosis by gossypol in an immortalized human alveolar lung cancer cell line [24].
• We found that gossypol, but not other Bcl-2-interacting molecules, induced cyto c release and loss of mitochondrial membrane potential (delta psi m) independently of mPTP and Bak/Bax activation [25].
• In gossypol-treated animals testis catalase and glutathione peroxidase activities were decreased [26].
• Gossypol inhibition of mitosis, cyclin D1 and Rb protein in human mammary cancer cells and cyclin-D1 transfected human fibrosarcoma cells [27].
• 3. RVD, the swelling-dependent chloride current and the depolarization seen after reducing extracellular osmolarity can be blocked by gossypol and NDGA (nordihydroguaiaretic acid), both structurally related to NPPB [28].

Analytical, diagnostic and therapeutic context of gossypol

• This was accompanied by a 41.6% mortality in the control group versus 8.3% in the gossypol-treated group [3].
• Five weeks after transplantation, tumor prevalence rate was 95.8% in the control group and 54.5% in the gossypol-treated group [3].
• CYP706B1 holds good potential for manipulation of gossypol levels in cottonseed via genetic engineering [29].
• The dissociation constants for the binding of the four compounds to human serum albumin were determined by fluorescence quenching titrations, and all four were found to have much lower affinities for albumin than the parent compound gossypol [30].
• The effect of gossypol upon organelles of rat sperm was investigated by light and electron microscopy [31].

References