Cordycepin-induced unfolded protein response-dependent cell death, and AKT/MAPK-mediated drug resistance in mouse testicular tumor cells

研究成果: Article

摘要

Testicular cancer is the most commonly diagnosed cancer in men at 15-44 years of age, and radical orchidectomy combined with chemotherapy is currently considered as the standard treatment. However, drugs resistance and side effects that impact the quality of life for patients with testicular cancer have not been markedly improved in recent decades. In this study, we characterized the pharmacological exacerbation of the unfolded protein response (UPR), which is an effective approach to kill testicular cancer cells, by carrying out a clustering analysis of mRNA expression profiles and the immunobloting examination of cordycepin-treated MA-10 cells. The UPR is executed in response to endoplasmic reticulum stress to complement by an apoptotic response if the defect cannot be resolved. Results showed that cordycepin significantly modulated FoxO/P15/P27, PERK-eIF2α (apoptotic), and the IRE1-XBP1 (adaptive) UPR pathways. Interestingly, a fraction of MA-10 cells survived after cordycepin treatment, the AKT, LC3 I/II, and MAPK signaling pathways were highly induced in attached cells as compared to the suspended cells, illustrating the drug resistance to cordycepin via activating AKT and MAPK pathways in MA-10 cells. In summary, PERK-eIF2α signaling pathway is required for pro-apoptotic UPR in MA-10 cell death following cordycepin treatment, suggesting a potential therapeutic application in treating testicular cancer. However, activation of AKT and MAPK pathways could possibly result in drug resistance to cordycepin in MA-10 cells.

原文English
頁(從 - 到)3949-3964
頁數16
期刊Cancer medicine
8
發行號8
DOIs
出版狀態Published - 2019 七月

指紋

Unfolded Protein Response
Testicular Neoplasms
Drug Resistance
Cell Death
Apoptosis Regulatory Proteins
Endoplasmic Reticulum Stress
Orchiectomy
Therapeutics
cordycepin
Drug-Related Side Effects and Adverse Reactions
Cluster Analysis
Quality of Life
Pharmacology
Drug Therapy
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

引用此文

@article{47f1a6694cda4e89853521a7f2079af6,
title = "Cordycepin-induced unfolded protein response-dependent cell death, and AKT/MAPK-mediated drug resistance in mouse testicular tumor cells",
abstract = "Testicular cancer is the most commonly diagnosed cancer in men at 15-44 years of age, and radical orchidectomy combined with chemotherapy is currently considered as the standard treatment. However, drugs resistance and side effects that impact the quality of life for patients with testicular cancer have not been markedly improved in recent decades. In this study, we characterized the pharmacological exacerbation of the unfolded protein response (UPR), which is an effective approach to kill testicular cancer cells, by carrying out a clustering analysis of mRNA expression profiles and the immunobloting examination of cordycepin-treated MA-10 cells. The UPR is executed in response to endoplasmic reticulum stress to complement by an apoptotic response if the defect cannot be resolved. Results showed that cordycepin significantly modulated FoxO/P15/P27, PERK-eIF2α (apoptotic), and the IRE1-XBP1 (adaptive) UPR pathways. Interestingly, a fraction of MA-10 cells survived after cordycepin treatment, the AKT, LC3 I/II, and MAPK signaling pathways were highly induced in attached cells as compared to the suspended cells, illustrating the drug resistance to cordycepin via activating AKT and MAPK pathways in MA-10 cells. In summary, PERK-eIF2α signaling pathway is required for pro-apoptotic UPR in MA-10 cell death following cordycepin treatment, suggesting a potential therapeutic application in treating testicular cancer. However, activation of AKT and MAPK pathways could possibly result in drug resistance to cordycepin in MA-10 cells.",
author = "Chang, {Ming Min} and Pan, {Bo Syong} and Wang, {Chia Yih} and Huang, {Bu Miin}",
year = "2019",
month = "7",
doi = "10.1002/cam4.2285",
language = "English",
volume = "8",
pages = "3949--3964",
journal = "Cancer Medicine",
issn = "2045-7634",
publisher = "John Wiley and Sons Ltd",
number = "8",

}

TY - JOUR

T1 - Cordycepin-induced unfolded protein response-dependent cell death, and AKT/MAPK-mediated drug resistance in mouse testicular tumor cells

AU - Chang, Ming Min

AU - Pan, Bo Syong

AU - Wang, Chia Yih

AU - Huang, Bu Miin

PY - 2019/7

Y1 - 2019/7

N2 - Testicular cancer is the most commonly diagnosed cancer in men at 15-44 years of age, and radical orchidectomy combined with chemotherapy is currently considered as the standard treatment. However, drugs resistance and side effects that impact the quality of life for patients with testicular cancer have not been markedly improved in recent decades. In this study, we characterized the pharmacological exacerbation of the unfolded protein response (UPR), which is an effective approach to kill testicular cancer cells, by carrying out a clustering analysis of mRNA expression profiles and the immunobloting examination of cordycepin-treated MA-10 cells. The UPR is executed in response to endoplasmic reticulum stress to complement by an apoptotic response if the defect cannot be resolved. Results showed that cordycepin significantly modulated FoxO/P15/P27, PERK-eIF2α (apoptotic), and the IRE1-XBP1 (adaptive) UPR pathways. Interestingly, a fraction of MA-10 cells survived after cordycepin treatment, the AKT, LC3 I/II, and MAPK signaling pathways were highly induced in attached cells as compared to the suspended cells, illustrating the drug resistance to cordycepin via activating AKT and MAPK pathways in MA-10 cells. In summary, PERK-eIF2α signaling pathway is required for pro-apoptotic UPR in MA-10 cell death following cordycepin treatment, suggesting a potential therapeutic application in treating testicular cancer. However, activation of AKT and MAPK pathways could possibly result in drug resistance to cordycepin in MA-10 cells.

AB - Testicular cancer is the most commonly diagnosed cancer in men at 15-44 years of age, and radical orchidectomy combined with chemotherapy is currently considered as the standard treatment. However, drugs resistance and side effects that impact the quality of life for patients with testicular cancer have not been markedly improved in recent decades. In this study, we characterized the pharmacological exacerbation of the unfolded protein response (UPR), which is an effective approach to kill testicular cancer cells, by carrying out a clustering analysis of mRNA expression profiles and the immunobloting examination of cordycepin-treated MA-10 cells. The UPR is executed in response to endoplasmic reticulum stress to complement by an apoptotic response if the defect cannot be resolved. Results showed that cordycepin significantly modulated FoxO/P15/P27, PERK-eIF2α (apoptotic), and the IRE1-XBP1 (adaptive) UPR pathways. Interestingly, a fraction of MA-10 cells survived after cordycepin treatment, the AKT, LC3 I/II, and MAPK signaling pathways were highly induced in attached cells as compared to the suspended cells, illustrating the drug resistance to cordycepin via activating AKT and MAPK pathways in MA-10 cells. In summary, PERK-eIF2α signaling pathway is required for pro-apoptotic UPR in MA-10 cell death following cordycepin treatment, suggesting a potential therapeutic application in treating testicular cancer. However, activation of AKT and MAPK pathways could possibly result in drug resistance to cordycepin in MA-10 cells.

UR - http://www.scopus.com/inward/record.url?scp=85069517452&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069517452&partnerID=8YFLogxK

U2 - 10.1002/cam4.2285

DO - 10.1002/cam4.2285

M3 - Article

C2 - 31145545

AN - SCOPUS:85069517452

VL - 8

SP - 3949

EP - 3964

JO - Cancer Medicine

JF - Cancer Medicine

SN - 2045-7634

IS - 8

ER -