A series of simple alpha, beta-unsaturated carbonyl compounds (1-26) was characterized for their cytotoxic profiles against oral human normal and
tumor cells. Several cycloalkenones showed potent cytotoxic activities against human
oral squamous cell carcinoma HSC-2 cell line. Among them, 4,4-dimethyl-2-cyclopenten-1-one (12) exhibited low cytotoxic activity against a normal human cell, gingival fibroblast HGF, and displayed higher
tumor-specific cytotoxicity (SI value = CC50 (HGF)/CC50 (HSC-2) = 4.0). The cytotoxicities of the unsaturated
lactones were moderately
tumor-specific (SI = 1.5-1.9).
Agarose gel electrophoresis showed that the induction of internucleosomal DNA fragmentation in human promyelocytic
leukemia cell HL-60 is dependent on the structure of alpha, beta-unsaturated carbonyl compounds. Fluorometric
protease assay showed that some, but not all compounds, activated the
caspase 3 in a dose-dependent manner. All alpha, beta-unsaturated carbonyl compounds studied did not activate
caspases 8 and 9. The cytotoxic activity of alpha, beta-unsaturated carbonyl compounds was profoundly reduced in the presence of
N-acetylcysteine. The study suggests that the presence of a non sterically hindered Michael acceptor seems to be an essential structural requirement for the cytotoxic activity in alpha, beta-unsaturated
ketones.