Dimethoxycurcumin, a Structural Analogue of Curcumin, Induces Apoptosis in Human Renal Carcinoma Caki Cells Through the Production of Reactive Oxygen Species, the Release of Cytochrome c, and the Activation of Caspase-3
Autor: | Hee Jong Jeong, Jea Whan Lee, Hye Min Hong, Dong Deuk Kwon, Hyun-Ock Pae |
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Jazyk: | angličtina |
Rok vydání: | 2010 |
Předmět: |
chemistry.chemical_classification
Reactive oxygen species Curcumin biology business.industry Cytochrome c Caspase 3 Apoptosis Pharmacology Metabolic stability Renal cell carcinoma chemistry.chemical_compound Investigative Urology Dimethoxycurcumin chemistry Antineoplastic agents biology.protein Medicine Original Article business Renal carcinoma |
Zdroj: | Korean Journal of Urology |
ISSN: | 2005-6745 2005-6737 |
Popis: | Purpose Curcumin (Cur) has been reported to induce apoptosis in human renal carcinoma Caki cells. Dimethoxycurcumin (DMC), one of several synthetic Cur analogues, has been reported to have increased metabolic stability over Cur. We determined whether DMC, like Cur, induces apoptosis in Caki cells and also compared the apoptosis-inducing activity of DMC with that of Cur. Materials and Methods Caki cells were treated with DMC possessing four methoxy groups, Cur possessing two methoxy groups, or bis-demethoxycurcumin (BMC), which lacks a methoxy group. Cell viability was measured by using a methyltetrazolium assay. Flow cytometry and the caspase-3 activity assay were used to detect apoptosis. The release of cytochrome-c (Cyt c) was detected by Western blot analysis. The production of reactive oxygen species (ROS) was measured by flow cytometry. Results DMC, Cur, and BMC reduced cell viability and induced apoptosis, but the potency varied; DMC was the most potent compound, followed by Cur and BMC. ROS production, Cyt c release, and caspase-3 activity were increased, again in the order DMC>Cur>BMC. N-Acetylcysteine, a potent antioxidant, inhibited ROS production, Cyt c release, caspase-3 activation, and apoptosis induction in DMC-treated cells. Conclusions These results indicate that DMC, like the original form of Cur, may induce apoptosis in human renal carcinoma Caki cells through the production of ROS, the release of mitochondrial Cyt c, and the subsequent activation of caspase-3. In addition, DMC is more potent than Cur in the ability to induce apoptosis. |
Databáze: | OpenAIRE |
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