Reactive oxygen species and p38 MAPK regulate Bax translocation and calcium redistribution in salubrinal-induced apoptosis of EBV-transformed B cells

Ga Bin Park; Yeong Seok Kim; Hyun Kyung Lee; Hyunkeun Song; Seonghan Kim; Dae Ho Cho; Dae Young Hur

doi:10.1016/j.canlet.2011.09.011

Reactive oxygen species and p38 MAPK regulate Bax translocation and calcium redistribution in salubrinal-induced apoptosis of EBV-transformed B cells

Ga Bin Park, Yeong Seok Kim, Hyun Kyung Lee, Hyunkeun Song, Seonghan Kim, Dae Ho Cho, Dae Young Hur

Research output: Contribution to journal › Article › peer-review

28 Citations (Scopus)

Abstract

Salubrinal is a specific eIF2α phosphatase inhibitor that inhibits ER stress-mediated apoptosis. However, maintaining hyper-phosphorylated eIF2α state with high doses of salubrinal treatment promotes apoptosis in some cancer cells. In this report, we found that salubrinal induced apoptosis of EBV-transformed B cells. Notably, salubrinal induced ROS generation and p38 MPAK activation, which then induced expression of FasL. Moreover, salubrinal subsequently led to activation of caspases, calcium redistribution, Bax translocation, cytochrome c release, and apoptosis. These findings suggest that salubrinal may be a novel therapeutic approach for EBV-associated malignant diseases.

Original language	English
Pages (from-to)	235-248
Number of pages	14
Journal	Cancer letters
Volume	313
Issue number	2
DOIs	https://doi.org/10.1016/j.canlet.2011.09.011
Publication status	Published - 2011 Dec 27
Externally published	Yes

Keywords

Apoptosis
B cell
Bax
Calcium
EBV
P38 MAPK
ROS
Salubrinal

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.canlet.2011.09.011

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title = "Reactive oxygen species and p38 MAPK regulate Bax translocation and calcium redistribution in salubrinal-induced apoptosis of EBV-transformed B cells",

abstract = "Salubrinal is a specific eIF2α phosphatase inhibitor that inhibits ER stress-mediated apoptosis. However, maintaining hyper-phosphorylated eIF2α state with high doses of salubrinal treatment promotes apoptosis in some cancer cells. In this report, we found that salubrinal induced apoptosis of EBV-transformed B cells. Notably, salubrinal induced ROS generation and p38 MPAK activation, which then induced expression of FasL. Moreover, salubrinal subsequently led to activation of caspases, calcium redistribution, Bax translocation, cytochrome c release, and apoptosis. These findings suggest that salubrinal may be a novel therapeutic approach for EBV-associated malignant diseases.",

keywords = "Apoptosis, B cell, Bax, Calcium, EBV, P38 MAPK, ROS, Salubrinal",

author = "Park, {Ga Bin} and Kim, {Yeong Seok} and Lee, {Hyun Kyung} and Hyunkeun Song and Seonghan Kim and Cho, {Dae Ho} and Hur, {Dae Young}",

note = "Funding Information: This work was supported by the SRC/ERC Program of MOST/KOSEF (Grant #: R11-2005-017) and the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea (Grant #: 0920040). ",

year = "2011",

month = dec,

day = "27",

doi = "10.1016/j.canlet.2011.09.011",

language = "English",

volume = "313",

pages = "235--248",

journal = "Cancer Letters",

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number = "2",

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TY - JOUR

T1 - Reactive oxygen species and p38 MAPK regulate Bax translocation and calcium redistribution in salubrinal-induced apoptosis of EBV-transformed B cells

AU - Park, Ga Bin

AU - Kim, Yeong Seok

AU - Lee, Hyun Kyung

AU - Song, Hyunkeun

AU - Kim, Seonghan

AU - Cho, Dae Ho

AU - Hur, Dae Young

N1 - Funding Information: This work was supported by the SRC/ERC Program of MOST/KOSEF (Grant #: R11-2005-017) and the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea (Grant #: 0920040).

PY - 2011/12/27

Y1 - 2011/12/27

N2 - Salubrinal is a specific eIF2α phosphatase inhibitor that inhibits ER stress-mediated apoptosis. However, maintaining hyper-phosphorylated eIF2α state with high doses of salubrinal treatment promotes apoptosis in some cancer cells. In this report, we found that salubrinal induced apoptosis of EBV-transformed B cells. Notably, salubrinal induced ROS generation and p38 MPAK activation, which then induced expression of FasL. Moreover, salubrinal subsequently led to activation of caspases, calcium redistribution, Bax translocation, cytochrome c release, and apoptosis. These findings suggest that salubrinal may be a novel therapeutic approach for EBV-associated malignant diseases.

AB - Salubrinal is a specific eIF2α phosphatase inhibitor that inhibits ER stress-mediated apoptosis. However, maintaining hyper-phosphorylated eIF2α state with high doses of salubrinal treatment promotes apoptosis in some cancer cells. In this report, we found that salubrinal induced apoptosis of EBV-transformed B cells. Notably, salubrinal induced ROS generation and p38 MPAK activation, which then induced expression of FasL. Moreover, salubrinal subsequently led to activation of caspases, calcium redistribution, Bax translocation, cytochrome c release, and apoptosis. These findings suggest that salubrinal may be a novel therapeutic approach for EBV-associated malignant diseases.

KW - Apoptosis

KW - B cell

KW - Bax

KW - Calcium

KW - EBV

KW - P38 MAPK

KW - ROS

KW - Salubrinal

UR - http://www.scopus.com/inward/record.url?scp=82655177994&partnerID=8YFLogxK

U2 - 10.1016/j.canlet.2011.09.011

DO - 10.1016/j.canlet.2011.09.011

M3 - Article

C2 - 22056078

AN - SCOPUS:82655177994

SN - 0304-3835

VL - 313

SP - 235

EP - 248

JO - Cancer Letters

JF - Cancer Letters

IS - 2

ER -

Reactive oxygen species and p38 MAPK regulate Bax translocation and calcium redistribution in salubrinal-induced apoptosis of EBV-transformed B cells

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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