Curcumin has been uncovered to inhibit CSN and block Mdm2 and E6 dependent p53 degradation. On top of that, in basal cell carcinoma, curcumin promotes de novo synthesis of p53 protein or another proteins for stabilization of p53, and consequently enhances its nuclear translocation to transactivate Cip1 and Gadd45 indicating that p53 linked signaling pathway is critically concerned in curcumin mediated apoptotic cell death. With time lapse video microg raphy and quantitative imaging strategy we now have dem onstrated that in deregulated cells, curcumin induces p53 significantly at G2 phase of cell cycle and enhances p53 DNA binding action leading to apoptosis at G2 phase. Over the other hand, curcumin increases p53 expression to a decrease extent through the entire cell cycle in non malignant cells. In these cells, curcumin revers ibly up regulates Cip1 expressions and inactivates pRB and consequently arrests them in G0 phase of cell cycle.
Consequently, these cells escape from curcumin induced apoptosis at G2 phase. Operates from other selleckchem laboratories also recommend that curcumin induces p53 expression in colon, breast, and other cancer cells. Reviews from our laboratory at the same time as from other laboratories suggest that curcumin pre dominantly acts within a p53 dependent method as careful analysis with the result of curcumin in several cells express ing wild sort or mutated p53 likewise as cells transfected with dominant damaging p53, exposed the cells expressing large amounts of wild variety p53 have been much more sensi tive to curcumin toxicity. To the other hand, p53 knock out likewise as p53 mutated cells Idarubicin also showed toxicity, while the apoptotic index is lower. Search for downstream of p53 uncovered that in mammary epithelial carcinoma and colon adenocarcinoma cells cur cumin could boost the expression on the pro apoptotic protein Bax and decrease the anti apoptotic protein Bcl 2/ Bcl xL through the phosphorylation at Ser15 and activa tion of p53.
Our effects also revealed curcumin induced G2/M arrest and apoptosis of mammary epithe lial carcinoma cells by way of p53 mediated Bax activation. Around the other hand, c Abl, a non receptor tyrosine kinase,

has become reported to perform an essential function in cur cumin induced cell death as a result of activation of JNK and induction of p53. Each one of these reports indicate that curcumin can induce cancer cell killing predominantly through p53 mediated pathway, p53 not just controls apoptotic pathways but also acts as a important cell cycle regulatory protein as it can trans activate cell cycle inhibitors like Cip1 around the occasion of DNA dam age while in proliferation and once the harm is irrepara ble it induces apoptosis by inducing the expression of professional apoptotic proteins like Bax. Thus far our discus sion thus clearly indicates the involvement of the guardian of genome, p53, in curcumin induced cancer cell apoptosis through cell cycle regulation.