Chrysin induces death of prostate cancer cells by inducing ROS and ER stress

Soomin Ryu, Whasun Lim, Fuller W. Bazer, Gwonhwa Song

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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-G1 phase 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 78kDa 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.

Original languageEnglish
JournalJournal of Cellular Physiology
DOIs
Publication statusAccepted/In press - 2017

Fingerprint

Endoplasmic Reticulum Stress
Reactive Oxygen Species
Prostatic Neoplasms
Cells
flavone
Proteins
Phosphotransferases
Prokaryotic Initiation Factor-2
Chemical activation
Eukaryotic Initiation Factor-2
Apoptosis
70-kDa Ribosomal Protein S6 Kinases
Eukaryotic Initiation Factors
Propolis
Unfolded Protein Response
S 6
Cell Line
Mitochondria
1-Phosphatidylinositol 4-Kinase
Honey

Keywords

  • Cell death
  • Chrysin
  • ER stress
  • Prostate cancer
  • ROS

ASJC Scopus subject areas

  • Medicine(all)
  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Chrysin induces death of prostate cancer cells by inducing ROS and ER stress. / Ryu, Soomin; Lim, Whasun; Bazer, Fuller W.; Song, Gwonhwa.

In: Journal of Cellular Physiology, 2017.

Research output: Contribution to journalArticle

@article{512802809d414b8cad76d4dc43550508,
title = "Chrysin induces death of prostate cancer cells by inducing ROS and ER stress",
abstract = "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-G1 phase 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 78kDa 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.",
keywords = "Cell death, Chrysin, ER stress, Prostate cancer, ROS",
author = "Soomin Ryu and Whasun Lim and Bazer, {Fuller W.} and Gwonhwa Song",
year = "2017",
doi = "10.1002/jcp.25861",
language = "English",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",

}

TY - JOUR

T1 - Chrysin induces death of prostate cancer cells by inducing ROS and ER stress

AU - Ryu, Soomin

AU - Lim, Whasun

AU - Bazer, Fuller W.

AU - Song, Gwonhwa

PY - 2017

Y1 - 2017

N2 - 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-G1 phase 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 78kDa 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.

AB - 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-G1 phase 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 78kDa 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.

KW - Cell death

KW - Chrysin

KW - ER stress

KW - Prostate cancer

KW - ROS

UR - http://www.scopus.com/inward/record.url?scp=85018358296&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018358296&partnerID=8YFLogxK

U2 - 10.1002/jcp.25861

DO - 10.1002/jcp.25861

M3 - Article

C2 - 28213961

AN - SCOPUS:85018358296

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

ER -