title: Induction of apoptosis by beta-diketones in human tumor cells.
abstract: 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.
authors.affiliation: Department of Dental Pharmacology, Meikai University School of Dentistry, Sakado, Saitama, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Nakano
authors.forename: Tohru
authors.initials: T
authors.lastname: Nakayachi
authors.forename: Eiji
authors.initials: E
authors.lastname: Yasumoto
authors.forename: Sufi Reza M D
authors.initials: SR
authors.lastname: Morshed
authors.forename: Ken
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kikuchi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Nishikawa
authors.forename: Kanji
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Osamu
authors.initials: O
authors.lastname: Amano
authors.forename: Masami
authors.initials: M
authors.lastname: Kawase
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakagami
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D007527:Isoenzymes; D007659:Ketones / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D007527:Isoenzymes; D007659:Ketones; D020169:Caspases