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Apoptosis-inducing effects of curcumin derivatives in human bladder cancer cells.
- Source :
-
Anti-cancer drugs [Anticancer Drugs] 2006 Mar; Vol. 17 (3), pp. 279-87. - Publication Year :
- 2006
-
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.
- Subjects :
- Caspase 3 metabolism
Cell Growth Processes drug effects
Cell Line, Tumor
Curcumin chemical synthesis
Curcumin chemistry
Epithelial Cells cytology
Epithelial Cells drug effects
Esterases metabolism
Growth Inhibitors pharmacology
Humans
Kidney Tubules cytology
Kidney Tubules drug effects
Urinary Bladder Neoplasms enzymology
Urinary Bladder Neoplasms pathology
Apoptosis drug effects
Curcumin analogs & derivatives
Curcumin pharmacology
Urinary Bladder Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0959-4973
- Volume :
- 17
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Anti-cancer drugs
- Publication Type :
- Academic Journal
- Accession number :
- 16520656
- Full Text :
- https://doi.org/10.1097/00001813-200603000-00006