Abstract
Protein kinase R (PKR) can suppress various types of solid tumors by inducing cellular oxidative stress and apoptosis. Likewise, Slaidorside, a plant flavonoid, was shown to have anti-tumorigenesis in many solid tumors.
This study evaluated anti-tumorigenesis of Salidroside in HT29 colorectal cancer and investigated if the underlying mechanism involves activation of PKR.
Control or PKR deficient cells were cultured in DMEM media treated with 100 μM Salidroside and cell survival, apoptosis, and other biochemical-related markers were evaluated.
Salidroside significantly reduced cell survival and proliferation and increased the release of lactate dehydrogenase (LDH) and levels of single-stranded DNA (ssDNA). It also increased the protein levels of caspases 3 and 8. Concomitantly, Salidroside increased the protein level and activity of PKR and increased the expression of its downstream targets, p-eIF2α (Ser51), p53 MAPK, and p53. On the contrary, it inhibited the nuclear activation of STAT-3 and NF-κB p65. In PKR deficient cells, the partial effects of Salidroside on cell survival, proliferation, and apoptotic markers were observed coincided with no effects on the expression of eIF-2α, and JNK, p53, p38 MAPK, and caspase 8 but with a significant decrease in the nuclear activities of STAT3 and NF-κB.
Salidroside suppresses the tumorigenesis of HT29 CRC by increasing activation of eIF-2α and JNK and upregulation of p53, p38 MAPK, and caspase-8 through upregulating and activation of PKR. However, the tumor suppressor effect of Salidroside requires also inhibition of STAT3 and NF-κB in a PKR-independent mechanism.