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.

In Vitro Growth Suppression of Renal Carcinoma Cells by Curcumin

“…Our observations are consistent with both in vitro and in vivo studies demonstrating a protective effect of curcumin on renal tubular epithelial cells. 30,31 Taken together, our data clearly showed that curcumin could be an effective growth suppressor of ccRCC cells. In most cases metastasis has already occurred when ccRCC is diagnosed.…”

Curcumin Analogue A501 induces G2/M Arrest and Apoptosis in Non-small Cell Lung Cancer Cells

“…Many studies have shown that curcumin or its analogues can induce tumour cells apoptosis (Tong et al, 2006;Selvendiran et al, 2007;Xiao et al, 2010;Prakobwong et al, 2011). Flow cytometry was used to determine whether the compound A501 can induce apoptosis of NSCLC cells.…”

Cellular uptake, retention and bioabsorption of HO-3867, a fluorinated curcumin analog with potential antitumor properties

“…[7][8][9] One potential means of circumventing these limitations is the development of synthetic analogs with enhanced bioabsorption and potency. [10][11][12][13] Recently, a novel class of curcumin analogs, namely diarylidenylpiperidone (DAP), has been synthesized by incorporating a piperidone ring in the beta-diketone backbone structure, as well as fluorinating the phenyl groups. [14][15][16] In a previous study, we compared the anticancer efficacy of four DAPs, named as H-4073, HO-3867, HO-4318 and HO-4200 with curcumin in a number of cancer as well non-cancerous (healthy) cell lines.…”