Rabbit Anti-Akt1 (N-Terminal) Polyclonal antibody

The current research seeks to examine the anticancer effect of polyisoprenoids from mangrove palm, Nypa fruticans, leaves in WiDr cells by analyzing the cell cycles of cancer and regulating the expression of p53, epidermal growth factor receptor (EGFR), PI3K, AKT1, and mammalian target of rapamycin (mTOR) genes by using the reverse transcription-polymerase chain reaction (RT-PCR). An inhibited cell cycle analysis was conducted using the flow cytometry, and the upregulation or downregulation of the expression of p53, EGFR, PI3K, AKT1, and mTOR genes was obtained using RT-PCR. The data were then statistically analyzed using one-way analysis of variance by a post hoc test, a parametric statistical analysis using Tukey's honest significant difference. Polyisoprenoids in N. fruticans extracts worked as chemotheraupetic in the G0-G1 cycle is 79.0%, however, with positive control 5-fluorouracil as 88.1% and are carried out by the specific upregulation of the expression of the p53 gene and the downregulation of the expression of the EGFR, PI3K, AKT1, and mTOR genes. This study can also explain the significant pharmacological properties of the leaves of the species N. fruticans that work specifically in the G0-G1 phase to upregulate the expression of the p53 gene and downregulate the expression of the EGFR, PI3K, AKT1, and mTOR genes. This study also revealed polyisoprenoid (100% dolichol), which blocked the growth and development of WiDr colon cancer cells.

The insulin-like growth factor 1 receptor (IGF-1R) governs several signaling pathways for cell proliferation, survival, and anti-apoptosis. Thus, targeting IGF-1R appears as a reasonable rationale for tumor treatment. However, clinical studies showed that inhibition of IGF-1R has very limited efficacy due to the development of resistance to IGF-1R blockade in tumor cells. Here, we discovered that prolonged treatment of colon cancer cells with IGF-1R inhibitors (BMS-754807 and GSK1838705A) stimulates p70 KDa ribosomal protein S6 kinase 1 (p70S6K1) activation, a well-known kinase signaling for cell survival. We also found that p70S6K1 activation by IGF-1R inhibition is independent of K-Ras and PIK3CA mutations that frequently occur in colon cancer. Besides the increased p70S6K1 phosphorylation, the phosphorylation of mitogen-activated protein kinase kinase 1 and 2 (MEK1/2) was elevated in the cells treated with BMS-754807. Interestingly, the increases in MEK1/2 and p70S6K1 phosphorylation were also observed when cells were subjected to the treatment of AKT inhibitor or genetic knockdown of AKT2 but not AKT1, suggesting that AKT2 inhibition stimulates MEK1/2 phosphorylation to activate p70S6K1. Conversely, inhibition of MEK1/2 by MEK1/2 inhibitor (U0126) or knockdown of MEK1 and MEK2 by correspondingmek1andmek2siRNA enhanced AKT phosphorylation, indicating mutual inhibition between AKT and MEK. Furthermore, the combination of BMS-754807 and U0126 efficiently decreased the cell viability and increased cleaved caspase 3 and apoptosis in vitro and in vivo. Our data suggest that the treatment of colon tumor cells with IGF-1R inhibitors stimulates p70S6K1 activity via MEK1/2 to promote survival, providing a new strategy for colorectal cancer therapeutics.