Induction of apoptosis by beta-diketones in human tumor cells.

A variety of beta-diketones were evaluated for their cytotoxic profiles against oral human normal and tumor cells. Among 22 compounds (BD1-22) tested, the cytotoxicity of 3-formylchromone (BD17) (CC50=7.8 microg/mL) against human oral squamous cell carcinoma (HSC-2) cells was higher than that of curcumin (CC50=23.6 microg/mL). Tumor cell-specific cytotoxicity was also detected in BD17 which exhibited little cytotoxic activity against a normal human cell, gingival fibroblast (HGF). (-)-3- (BD13) (CC50=21.7 microg/mL) and (+)-3-(Trifluoroacetyl)camphor (BD12) (CC50=29.7 microg/mL) are enantiomers and showed cytotoxicity comparable to curcumin and dibenzoylmethane (BD2) (CC50=22.5 microg/mL). BD13 did not induce DNA fragmentation in HL-60 cells nor activate caspase 3, 8 and 9 in both HL-60 and HSC-2 cells, regardless of the presence or absence of FeCl3. On the other hand, BD17 was found to induce apoptosis in HSC-2 and HL-60 cells, as judged by internucleosomal DNA fragmentation, caspase 3, 8 and 9 activation and dysfunction of mitochondrial membrane potential. The cytotoxic activity of BD13, BD17 and curcumin was significantly reduced by chelation with FeCl3. The tumor-specific cytotoxicity and apoptosis-inducing activity of BD17 against human tumor cells undoubtedly warrant further studies of its efficacy as a cancer chemotherapeutic agent.