p53 independent pathways and curcumin Its evident that curcumin can induce selective cancer cell killing inside a p53 dependent method, but impaired p53 expression or activity is connected to several different neo plastic transformations. Expanding reviews are indicating that curcumin can block cell cycle progression or maybe apoptosis within a p53 independent manner at the same time, espe cially within the cells that lack practical p53. Curcumin induces apoptosis in p53 null lung cancer cells. It induces melanoma cell apoptosis by activating caspase 8 and caspase three by means of Fas receptor aggregation in the FasL inde pendent method, blocks NF B cell survival pathway and suppresses the apoptotic inhibitor XIAP. Curcumin inhibits cellular isopeptidases, and trigger cell death inde pendently of p53 in isogenic pairs of RKO and HCT 116 cells with differential p53 standing.
It enhances the chemotherapy induced cytotoxicity in p53 null prostate cancer cell line Pc 3, by means of up regulation of Cip1 and C/ EBP expressions and suppression of NF B activation. In addition, it induces apoptosis in multiple myloma cells by inhibiting IKK and NF B exercise. Review indicates that curcumin down regulates NF B and AP 1 exercise in androgen dependent and independent prostate cancer cell lines. Curcumin is you can find out more a potent inhibitor of protein kinase C, EGF receptor tyrosine kinase and IB kinase. Subsequently, curcumin inhibits the oncogenes as well as c jun, c fos, c myc, NIK, MAPKs, ELK, PI3K, Akt, CDKs and iNOS. In con trast on the pointed out reviews, research by Collet et al. displays that curcumin induces JNK dependent apoptosis of colon cancer cells and it may possibly induce JNK dependent sus tained phosphorylation of c jun and stimulation of AP 1 transcriptional exercise.
The oxidized type of JNJ-1661010 cancer chemopreventive agent curcumin can inactivate PKC by oxidizing the vicinal thiols current within the catalytic domain within the enzyme. Latest scientific studies indicated that proteasome mediated degradation of cell proteins play a pivotal role inside the regulation of a few simple cellular proc esses like differentiation, proliferation, cell cycling, and apoptosis. It has also been demonstrated that curcu min induced apoptosis is mediated with the impair ment of ubiquitin proteasome pathway. Every one of these reviews suggests that curcumin can induce apoptosis or block cell cycle progression inside a number of cancer cell lines, predominantly through p53 dependent pathways, nonetheless it also can act inside a p53 independent method. Other functions of curcumin Curcumin inhibits angiogenesis right and by way of regula tion of angiogenic development variables like

vascular endothelial development factor, basic fibroblast growth aspect and epider mal development issue, likewise because the genes like angiopoietin one and two, hypoxia inducible factor 1, heme oxygenase 1, and the transcriptional variables like NF B.