Cytotoxicity of enantiomers of gossypol

Joseph, A.E.A.; Matlin, Stephen A.; Knox, P. P.

doi:10.1038/bjc.1986.205

Cited by 75 publications

(33 citation statements)

References 7 publications

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“…This has been confirmed by the report that pretreatment of plasma with 2,4-dinitrofluorobenzene or aspirin which acrylates or acetylates the amino groups of protein can slow down the rate of disappearance of the free (-) gossypol in plasma (Wu & Reidenberg, 1990 (Haspel et ai, 1984;Joseph et at, 1986;Tanphaichtr et at, 1988). The EC50 for ( -) gossypol was much lower than that of ( + ) gossypol in the presence of serum protein.…”

Section: Discussionsupporting

confidence: 63%

Differential binding of (+) and (-) gossypol to plasma protein and their entry into rat testis

Wang

Tao²,

Wu³

et al. 1992

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Summary. Concentrations of ( + )and ( \ m=-\ ) gossypol were measured by high performance liquid chromatography after they were incubated with plasma proteins in vitro. The concentration of ( \m=-\) gossypol decreased more than the concentration of ( + ) gossypol. A similar decrease in free gossypol concentrations in the blood plasma of rats was observed after intravenous infusion of gossypol enantiomers. The concentration of ( \ m=-\ ) gossypol was also found to be lower than the concentration of ( + ) gossypol at the blood\p=n-\testisbarrier. The biological effect of ( \ m=-\ ) gossypol probably results from its stereospecific binding to extra-and intracellular proteins in vivo and inhibition of the biological activity of some proteins.

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Section: Discussionsupporting

confidence: 63%

Differential binding of (+) and (-) gossypol to plasma protein and their entry into rat testis

Wang

Tao²,

Wu³

et al. 1992

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“…has long been recognized as an anti-fertility agent and, more recently, it has been demonstrated to inhibit the growth of various carcinoma cell lines in vitro (Floridi et al, 1983;Joseph et al, 1983;Haspel et al, 1984; Tuszynski and Cossu, 1984;Band et al, 1989;Benz et al, 1990;Jaroszewski et al, 1990) and in vivo (Wu et al, 1989;Rao et al, 1985) including oestrogen-sensitive (MCF-7 and MCF-7 Adr) and -insensitive (MDA-MB-231) human mammary cancer cells (Hu et al, 1993;Gilbert et al, 1995). Clinically, gossypol has been efficacious in the treatment of metastatic adrenal cancer (Flack et al, 1993), holding promise as an anti-tumour agent.…”

mentioning

confidence: 99%

Gossypol inhibition of mitosis, cyclin D1 and Rb protein in human mammary cancer cells and cyclin-D1 transfected human fibrosarcoma cells

Ligueros

Jeoung²,

Tang³

et al. 1997

Br J Cancer

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Summary The antiproliferative effects of gossypol on human MCF-7 mammary cancer cells and cyclin Dl-transfected HT-1060 human fibrosarcoma cells were investigated by cell cycle analysis and effects on the cell cycle regulatory proteins Rb and cyclin Dl. Flow cytometry of MCF-7 cells at 24 h indicated that 10 gm gossypol inhibited DNA synthesis by producing a G,/S block. Western blot analysis using antihuman Rb antibodies and anti-human cyclin Dl antibodies in MCF-7 cells and high-and low-expression cyclin Dl-transfected fibrosarcoma cells indicated that, after 6 h exposure, gossypol decreased the expression levels of these proteins in a dose-dependent manner. Gossypol also decreased the ratio of phosphorylated to unphosphorylated Rb protein in human mammary cancer and fibrosarcoma cell lines. Gossypol (10 gM) treated also decreased cyclin D1-associated kinase activity on histone Hi used as a substrate in MCF-7 cells. These results suggest that gossypol might suppress growth by modulating the expression of cell cycle regulatory proteins Rb and cyclin Dl and the phosphorylation of Rb protein.

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“…The ( -)-enantiomer of gossypol but not the ( + )-enantiomer inhibits proliferation of normal fibroblasts and tumour-derived cells (Joseph et al, 1986). This indicates that the toxicity of ( -)gossypol is not cell specific.…”

Section: Discussionmentioning

confidence: 96%

Differential effects of (+)- and (-)-gossypol enantiomers on LDH-C4 activity of hamster spermatogenic epithelium in vitro

Boer

Grootegoed²

1988

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Tubular fragments (spermatogenic epithelium) from immature hamsters were isolated and cultured with low doses of (+)- and (-)-gossypol enantiomers. The activity of lactate dehydrogenase isoenzyme LDH-C4 was estimated as a marker for spermatogenic cell development and alpha-ketoisovalerate was used as the substrate. In the absence of gossypol, the specific activity of LDH-C4 in the tubular fragments was increased 40% during incubation for 48 h. This developmental increase was suppressed by gossypol. The specific activity of LDH-C4 in the tubular fragments was lowered by gossypol, after 48 h of culture in the presence of low doses of racemic gossypol (1-4 microM) and 1% fetal calf serum. In this in-vitro system the (-)-enantiomer but not the (+)-enantiomer of gossypol affected the LDH-C4 activity. This is in agreement with other reports showing that only the (-)-enantiomer induces infertility. The observed action of gossypol on LDH-C4 activity in the tubular fragments may reflect gossypol-induced degeneration of spermatogenic cells. The present in-vitro system can be used to estimate the actions of gossypol derivatives, other investigational antifertility agents, and toxic agents on the spermatogenic epithelium.

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Cytotoxicity of enantiomers of gossypol

Cited by 75 publications

References 7 publications

Differential binding of (+) and (-) gossypol to plasma protein and their entry into rat testis

Differential binding of (+) and (-) gossypol to plasma protein and their entry into rat testis

Gossypol inhibition of mitosis, cyclin D1 and Rb protein in human mammary cancer cells and cyclin-D1 transfected human fibrosarcoma cells

Differential effects of (+)- and (-)-gossypol enantiomers on LDH-C4 activity of hamster spermatogenic epithelium in vitro

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