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KMID : 0366220080430010019
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Korean Journal of Hematology
2008 Volume.43 No. 1 p.19 ~ p.27
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Abrogation of U266 Multiple Myeloma Cell Proliferation Via Inhibition of NF-?B Activation by Curcumin
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Park Ju-Won
Ahn Kwang-Sung
Kim Byoung-Kook
Yoon Sung-Soo
Kim Dae-Young
Bae Eun-Kyung
Kim Jin-Ho
Jung Seung-Hyeon
Kim Byung-Su
Lee Young-Yiul
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Abstract
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Background:Curcumin is a naturally occurring biologically active compound, and it has been shown to possess potent anti-inflammatory, anti-tumor and anti-oxidative properties. It is known for its anti-proliferative and proapoptotic effects in several cancer cells. Curcumin\’s effects on the mechanisms of cell survival and the expression of various cytokines were investigated in U266 cells and the in vivo effects of curcumin were examined using an animal model.
Methods:Cell proliferation assay and flow cytometry were used to examine cell proliferation, along with cell cycle analysis. The protein expressions were analyzed by Western blotting and the expressed levels of cytokines were analyzed by the ELISA method.
Results:Curcumin inhibited U266 cell growth in a dose-dependent and time-dependent manner. Cell cycle analysis showed an increased sub-G1 phase, a down regulated cyclinD1 expression and an induced p21 expression. Apoptosis induced a down regulated procaspase 3 expression and it induced cleaved PARP. Curcumin inhibited the IL (interleukin)-6 induced cell signal pathway via decreasing the STAT1 an 3, Erk cyclinD1 and c-myc expressions. Also, administration of 25mg/kg curcumin to a U266 animal model inhibited cancer cell engraftment in the bone marrow and it decreased the IL-6, sIL-6R and IL-8 expression levels.
Conclusion:Curcumin induced cell cycle arrest and apoptosis and it inhibited the IL-6 mediated signal transduction pathways in U266 cells. Similar to the in vitro results, curcumin inhibited cancer cell proliferation and the expression of cytokine in vivo.
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KEYWORD
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Curcumin, 6-aminoquinazoline, Multiple myeloma, Animal model, IL-6, sIL-6R
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