A study of the role of cell cycle events mediating the action of coumarin derivatives in human malignant melanoma cells

Cancer Letters
Gregory J FinnDenise A Egan

Abstract

6-Nitro-7-hydroxycoumarin (6-NO2-7-OHC) and 3,6,8-trinitro-7-hydroxycoumarin (3,6,8-NO2-7-OHC) have previously been shown to be potent and selective anti-proliferative agents to the human skin cell line, SK-MEL-31. Here, we investigate the reversibility of their cytotoxicity, along with their effects on DNA synthesis and cell cycle events. Comparative studies were carried out using the main metabolite of coumarin in man, 7-hydroxycoumarin (7-OHC). 6-NO2-7-OHC and 3,6,8-NO2-7-OHC, were found to be irreversible cytotoxic agents, unlike 7-OHC. All three derivatives inhibited DNA synthesis, but 7-OHC was only nitro-derivatives which acted in an irreversible manner. Flow cytometric studies demonstrated that both nitro-derivatives caused a dose- and time-dependant S phase accumulation. 7-OHC exerted a similar effect, but appeared to be less potent. Finally, the two nitro-derivatives caused a dose-dependant inhibition of the S phase regulatory protein, cyclin A. Consequently, these and other nitro-derivatives of 7-OHC may represent novel therapeutic agents for the treatment of malignant melanoma as they are capable of selective and irreversible cytotoxicity.

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Citations

Sep 14, 2012·Applied Biochemistry and Biotechnology·Mahmut ErzenginSelma Sinan
Jan 1, 2009·Acta Crystallographica. Section E, Structure Reports Online·Cui-Lian XuMing-Qin Zhao
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Jan 1, 2010·Acta Crystallographica. Section E, Structure Reports Online·Afsheen ArshadHoong-Kun Fun
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