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: Qiang-Song Tong, Li-Duan Zheng, Peng Lu, Feng-chao Jiang, Fang-Min Chen, Fu-Qing Zeng, Liang Wang, Ji-Hua Dong
• Journal: Anti-cancer drugs (Anticancer Drugs) Vol. 17 Issue 3 Pg. 279-87 (Mar 2006) ISSN: 0959-4973 [Print] England
• PMID: 16520656 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Growth Inhibitors
• Esterases
• Caspase 3
• Curcumin

Topics

• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Cell Growth Processes (drug effects)
• Cell Line, Tumor
• Curcumin (analogs & derivatives, chemical synthesis, chemistry, pharmacology)
• Epithelial Cells (cytology, drug effects)
• Esterases (metabolism)
• Growth Inhibitors (pharmacology)
• Humans
• Kidney Tubules (cytology, drug effects)
• Urinary Bladder Neoplasms (drug therapy, enzymology, pathology)