Cytotoxicity of gossypol enantiomers and its quinone metabolite gossypolone in melanoma cell lines.

Abstract

The cytotoxicity of the (-)- and (+)-isomers and the quinone metabolite gossypolone prepared from the naturally occurring polyphenolic dialdehyde gossypol were compared using two human melanoma cell lines (SK-mel-19 and SK-mel-28) with a similar growth rate, one melanotic (melanin content of 69 pg/cell) and one amelanotic (melanin content of 10 pg/cell). Results from two viability assays (MTT and flow cytometry) showed that the cytotoxicity of racemic gossypol was identical for both cell lines (50% inhibition of cell growth IC50 = 22 microM). Gossypolone at equimolar concentrations was inactive in the amelanotic cell line and as potent as racemic gossypol in the melanotic cell line. (-)-Gossypol was significantly more active in both cell lines compared with the (+)-isomer. The cytotoxic effect of (-)-gossypol was both concentration and time dependent. Under serum-free conditions, the cytotoxicity of both enantiomers was increased, suggesting that serum protein binding may play a role in the differential toxicity of these isomers in vitro. Morphological changes after exposure to (-)-gossypol included shrinkage and loss of adherence. Cell sensitivity to the (-)-isomer was five-fold greater (IC50 = 4 microM) using a clonogenic assay. At equimolar concentrations, (-)-gossypol was more cytotoxic to both cell lines than the clinically used drugs cisplatin, dacarbazine and melphalan. The results of this study suggest that (-)-gossypol may be of potential therapeutic benefit in melanoma patients.

• Authors: L Blackstaffe, M D Shelley, R G Fish
• Journal: Melanoma research (Melanoma Res) Vol. 7 Issue 5 Pg. 364-72 (Oct 1997) ISSN: 0960-8931 [Print] England
• PMID: 9429219 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• gossypolone
• Gossypol

Topics

• Cell Adhesion
• Cell Division (drug effects)
• Cell Line
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Gossypol (analogs & derivatives, toxicity)
• Humans
• Melanoma (pathology, ultrastructure)
• Microscopy, Electron, Scanning
• Stereoisomerism
• Tumor Cells, Cultured