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Inhibition Of Curcumin On Proliferation Of Glioma C6 Through Modulation Of NF-kappaB And Bcl-2/Bax Expression

Posted on:2008-05-05Degree:MasterType:Thesis
Country:ChinaCandidate:D Y SongFull Text:PDF
GTID:2144360212497214Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
The antitumor activity of drug is associated with inhibition of tumor cell proliferation, promotion of cellular differentiation, and induction of apoptosis. Curcumin (diferuloylmethane) is a lowmolecular weight polyphenol, it is the active constituent of turmeric. It has been shown to possess antitumor properties and other pharmacological activity, such as anti-inflammatory, antivirus, antioxidant, scavenging of oxygen free radical and ant-fibrosis. the mechanism of drug action is more complicated but one of them has even been attributed to the increased expression and activation of transcription factor, antitumor mechanisms of curcumin is still to be elucidated. So in this study, glioma cell line C6 was treated with curcumin, and NF-κB, Bcl-2 and Bax was determined, and it was discussed that curcumin induced apoptosis of tumor cells.Methods:It was observed that effect of curcumin on the proliferation or apoptosis of glioma cell C6 through MTT and morphocytological method. Intracellular GSH level was analyzed by spectrophotometry. The expression of Bcl-2, Bax and IκB mRNA was analyzed by RT-PCR method, the expression of p65 and p50 of NF-κB subunits was also determind with western blottin method. Results:After 6h of curcumin treatment, visible morphocytological changes of tumor cells was observed. It was observed that enlarged cell space, poor adherence, pyknosis, abnormal shape, membrane blebbing, and more dead cell floating in medium. And this suggests that curcumin inhibits the proliferation of tumor cell and induces apoptosis.Intracellular GSH level increased when C6 cells exposed to curcumin.The results of Western blotting showed that the expression of p65 and p50 of NF-κB subunits deceased after curcumin treatment, but the increased level of IκB mRNA was showed by RT-PCR method. curcumin treatment also resulted in the decreased bcl-2 and increased bax mRNA expression.Discussion:NF-κB pathways are key regulators of numerous cellular events such as proliferation, differentiation, and apoptosis, and it is also related with tumor development and progression. In this study, it was proven that NF-κB participates in the modulation of apoptosis of C6 cell induced by curcumin. IκB not only inhibit the activity of NF-κB, but also induce the dissociation of NF-κB from DNA, terminate the transcription process mediated with NF-κB. When glioma cell C6 is treated with curcumin, increased IκB can inhibit NF-κB activation, and curcumin can also inhibit NF-κB expression, and both these induce the apoptosis of glioma cell C6.The expression of anti-apoptotic bcl-2 and pro-apoptotic bax or their proportion is very important for tumor cell survive, they regulated the release of cytochrome C and caspases from mitochondria, then control the fate of tumor cells. The decreased expression of Bcl-2 and increased bax induced by curcumin is involved in apoptotic process of glioma cells.The increased level of intracellular GSH in C6 cell treated with curcumin is a compensatory reaction and maybe involved in protection of tumor cell from oxidative injury.So it can be postulated that NF-κB activation and expression is involved in the mechanisms of proliferation inhibition and apoptosis induction of curcumin on glioma cell C6, Bcl-2/Bax participated in this event. Conclusion:Curcumin can inhibit the proliferation and induce apoptosis of glioma cell C5 in a dose dependent manner. The upregulated IκB and downregulated NF-κB may modulate the expression of Bcl-2 and bax, then control the cell survival/death decision.
Keywords/Search Tags:Curcumin, glioma cell, apoptosis
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