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KMID : 0358320100510120870
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Korean Journal of Urology
2010 Volume.51 No. 12 p.870 ~ p.878
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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
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Lee Jea-Whan
Hong Hye-Min
Kwon Dong-Deuk
Pae Hyun-Ock
Jeong Hee-Jong
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Abstract
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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.
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KEYWORD
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Antineoplastic agents, Apoptosis, Curcumin, Dimethoxycurcumin, Renal cell carcinoma
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