title: Apoptosis-inducing effects of curcumin derivatives in human bladder cancer cells.
abstract: Our aim was to prepare curcumin derivatives and study their apoptosis-inducing effects on bladder cancer cells in order to establish a basis for targeted chemotherapy of cancer. n-Maleoyl-L-valine-curcumin (NVC) and n-maleoyl-glycine-curcumin (NGC) were chemically synthesized. Intracellular esterase activity of the human bladder cancer EJ cell line and renal tubular epithelial (HKC) cells was examined by 6-carboxyfluorescein diacetate fluorometry. After incubation with NVC or NGC for 6-24 h, cell viability was detected by MTT colorimetry. Cell apoptosis and apoptotic rates were measured by acridine orange/ethidium bromide staining, TUNEL labeling and flow cytometry. Intracellular caspase-3 activities were determined by spectrophotometry. The esterase activity within EJ cells was 10.2-fold higher than that of HKC cells, which was abolished by bis-p-nitrophenylphosphate, an esterase inhibitor, resulting in decreases in NVC- and NGC-mediated cell viability arrest. For EJ cells, the IC50 values of NVC (20.1 micromol/l) and NGC (18.7 micromol/l) were close to curcumin (16.5 micromol/l). Meanwhile, their IC50 values on HKC cells were, respectively, 4.06- and 3.23-fold higher than curcumin. Moreover, NVC and NGC induced apoptosis of EJ cells by 10.13-23.36 and 12.42-28.56%, respectively. Administration of these two derivatives resulted in decreased apoptosis of HKC cells compared with curcumin. The caspase-3 activities of EJ cells, but not of HKC cells, were 5.21- and 5.63-fold enhanced by NVC and NGC, respectively. Thus, novel esterase-sensitive curcumin derivatives were synthesized, which induced extensive apoptosis of bladder cancer EJ cells, but not normal cells.
authors.affiliation: Department of Surgery, Union Hospital of Tongji Medical College, Wuhan, Hubei Province, China. qstong@mails.tjmu.edu.cn
authors.forename: Qiang-Song
authors.initials: QS
authors.lastname: Tong
authors.forename: Li-Duan
authors.initials: LD
authors.lastname: Zheng
authors.forename: Peng
authors.initials: P
authors.lastname: Lu
authors.forename: Feng-chao
authors.initials: FC
authors.lastname: Jiang
authors.forename: Fang-Min
authors.initials: FM
authors.lastname: Chen
authors.forename: Fu-Qing
authors.initials: FQ
authors.lastname: Zeng
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Ji-Hua
authors.initials: JH
authors.lastname: Dong
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D003474:Curcumin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D004950:Esterases / Q000378:metabolism; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology
chemical_list: D006131:Growth Inhibitors; D004950:Esterases; D053148:Caspase 3; D003474:Curcumin