incubation of PC 3 cells with curcumin changed neither the protein level or the state of PP2A C subunit. Next the cellular protein phosphatase exercise upon curcumin FK866 concentration treatment was dependant on Malachite Green Phosphatase assay. As shown in Fig. 6D, incubation of PC 3 cells with curcumin for 10 min attention dependently improved the protein phosphatase activity in the cell extract, and this curcumin triggered activity might be inhibited by calyculin A. Taken together, these data show that incubation with curcumin triggered PP2A and/or unspecified calyculin A sensitive and painful protein phosphatase, and led to dephosphorylation of Akt, mTOR, and their downstream substrates. Conversation Curcumin has been demonstrated to prevent the phosphorylation and activation of Akt in PC 3 cells, nevertheless, the effects of curcumin on the downstream signaling of Akt have not been investigated. In today’s research we firstly PTM demonstrated that curcumin also inhibited the phosphorylation of Akt substrates GSK3, FKHR1, TSC2, mTOR as well as mTOR downstream targets 4E BP1, eIF4G, p70 S6K and S6 in a similar concentration dependent manner as with Akt. In support of the role of Akt/mTOR signaling in the get a grip on of protein synthesis, curcumin inhibited protein synthesis and then DNA synthesis in PC 3 cells, and these inhibitions could possibly be partly but considerably rescued by over-expression of Akt or by repair of Akt/mTOR signaling by calyculin A. Cyclin D1, which will be critical for cell proliferation, has been reported to be controlled by Akt/mTOR posttranscriptionally. In PC 3 cells the expression of cyclin D1 was also inhibited by curcumin and could be repaired by over-expression of Akt or by calyculin A. These are consistent with the important functions of Akt/mTOR signaling in cell survival and expansion. Curcumin has been claimed to inhibit Akt/mTOR signaling in other cancer cells, but the underlying mechanism purchase Dabrafenib remains unknown. One important aim of this study would be to determine the molecular mechanism by which curcumin inhibits Akt/mTOR signaling. Firstly we examined the consequence of curcumin on the p85 subunit of PI3K. The phosphorylation of p85 in PC 3 cells is barely noticeable and wasn’t suffering from curcumin treatment. LY294002, a specific PI3K inhibitor, inhibited the phosphorylation of mTOR and Akt, and this inhibition could be restored by addition of exogenous PIP3. In contrast, exogenous PIP3 did not restore curcumin mediated inhibition. More over, it’s been well-documented that in several cancer cells including PC 3 cells, the activation of Akt/mTOR signaling axis is less influenced by upstream signals due to lack of PTEN function. Really, as noted by others and confirmed in our research, curcumin also inhibited Akt/mTOR signaling and growth in DU145 prostate cancer cells which carry wt PTEN. Taken together, these facts propose that curcumin inhibits Akt/mTOR signaling at downstream of PI3K.