Chrysin induces death of prostate cancer cells by inducing ROS and ER stress. - GreenMedInfo Summary
Chrysin induces death of prostate cancer cells by inducing ROS and ER stress.
J Cell Physiol. 2017 Dec ;232(12):3786-3797. Epub 2017 May 3. PMID: 28213961
Chrysin is a natural flavone found in numerous plant extracts, honey, and propolis that has multiple biological activities including anti-cancer effects. Understanding of biological mechanisms mediated in response to chrysin in cancerous cells may provide novel insight into chemotherapeutic approaches with reduced side effects in cancers. In the present study, we investigated functional roles of chrysin in progression of prostate cancer cells using DU145 and PC-3 cell lines. The results showed that chrysin induced apoptosis of cells evidenced by DNA fragmentation and increasing the population of both DU145 and PC-3 cells in the sub-Gphase of the cell cycle. In addition, chrysin reduced expression of proliferating cell nuclear antigen in the prostate cancer cell lines compared to untreated prostate cancer cells. Moreover, chrysin induced loss of mitochondria membrane potential (MMP), while increasing production of reactive oxygen species (ROS) and lipid peroxidation in a dose-dependent manner. Also, it induced endoplasmic reticulum (ER) stress through activation of unfolded protein response (UPR) proteins including PRKR-like ER kinase (PERK), eukaryotic translation initiation factor 2α (eIF2α), and 78 kDa glucose-regulated protein (GRP78) in DU145 and PC-3 cells. The chrysin-mediated intracellular signaling pathways suppressed phosphoinositide 3-kinase (PI3K) and the abundance of AKT, P70S6K, S6, and P90RSK proteins, but stimulated mitogen-activated protein kinases (MAPK) and activation of ERK1/2 and P38 proteins in the prostate cancer cells. Collectively, these results indicate that chrysin initiates cell death through induction of mitochondrial-mediated apoptosis and ER stress, and regulation of signaling pathways responsible for proliferation of prostate cancer cells.