Cobalt chloride treatment induces autophagic apoptosis in human glioma cells via a p53-dependent pathway

Bor Chin Cheng, Jui Tai Chen, Shun Tai Yang, Chung Ching Chio, Shing Hwa Liu, Ruei Ming Chen

研究成果: 雜誌貢獻文章

10 引文 (Scopus)

摘要

Malignant glioma is the most aggressive brain tumor. Hypoxic condition has been explored for killing cancer stem cells or drug-resistant tumor cells. This study investigated the effects of hypoxia on autophagic death and the possible mechanisms. Exposure of human malignant glioma U87-MG cells to cobalt chloride (CoCl2) increased cellular hypoxia-inducible factor-1α levels and concurrently decreased cell viability concentration-and time-dependently. In parallel, treatment with CoCl2 suppressed proliferation of human U87-MG cells. Autophagic cells and levels of LC3-II were concentration-and time-dependently induced in human U87-MG cells after exposure to CoCl2. However, pretreatment with 3-mehyladenine (3-MA) and chloroquine, inhibitors of cell autophagy, caused significant alleviations in CoCl2-induced cell autophagy. In contrast, exposure to rapamycin, an inducer of cell autophagy, synergistically induced hypoxiainduced autophagy of U87-MG cells. Administration of human U87-MG cells with CoCl2 triggered caspase-3 activation and cell apoptosis. Interestingly, pretreatment with 3-MA and chloroquine remarkably suppressed CoCl2-induced caspase-3 activation and cell apoptosis. Application of p53 small interference (si)RNA into human U87-MG cells downregulated levels of this protein and simultaneously lowered hypoxiaand 3-MA-induced alterations in cell autophagy, apoptosis, and death. The hypoxia-induced autophagy and apoptosis of DBTRG-05MG cells were significantly lowered by 3-MA pretreatment and p53 knockdown. Therefore, the present study shows that CoCl2 treatment can induce autophagy of human glioma cells and subsequent autophagic apoptosis via a p53-dependent pathway. Hypoxia-induced autophagic apoptosis may be applied as a therapeutic strategy for treatment of glioma patients.
原文英語
頁(從 - 到)964-974
頁數11
期刊International Journal of Oncology
50
發行號3
DOIs
出版狀態已發佈 - 三月 1 2017

指紋

Glioma
Apoptosis
Autophagy
Chloroquine
cobaltous chloride
Caspase 3
Hypoxia-Inducible Factor 1
Cell Hypoxia
Neoplastic Stem Cells
Sirolimus
Therapeutics
Helper-Inducer T-Lymphocytes
RNA Interference
Brain Neoplasms
Cell Survival
Down-Regulation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

引用此文

Cobalt chloride treatment induces autophagic apoptosis in human glioma cells via a p53-dependent pathway. / Cheng, Bor Chin; Chen, Jui Tai; Yang, Shun Tai; Chio, Chung Ching; Liu, Shing Hwa; Chen, Ruei Ming.

於: International Journal of Oncology, 卷 50, 編號 3, 01.03.2017, p. 964-974.

研究成果: 雜誌貢獻文章

@article{3394209278f1440fa79af3aa86560029,
title = "Cobalt chloride treatment induces autophagic apoptosis in human glioma cells via a p53-dependent pathway",
abstract = "Malignant glioma is the most aggressive brain tumor. Hypoxic condition has been explored for killing cancer stem cells or drug-resistant tumor cells. This study investigated the effects of hypoxia on autophagic death and the possible mechanisms. Exposure of human malignant glioma U87-MG cells to cobalt chloride (CoCl2) increased cellular hypoxia-inducible factor-1α levels and concurrently decreased cell viability concentration-and time-dependently. In parallel, treatment with CoCl2 suppressed proliferation of human U87-MG cells. Autophagic cells and levels of LC3-II were concentration-and time-dependently induced in human U87-MG cells after exposure to CoCl2. However, pretreatment with 3-mehyladenine (3-MA) and chloroquine, inhibitors of cell autophagy, caused significant alleviations in CoCl2-induced cell autophagy. In contrast, exposure to rapamycin, an inducer of cell autophagy, synergistically induced hypoxiainduced autophagy of U87-MG cells. Administration of human U87-MG cells with CoCl2 triggered caspase-3 activation and cell apoptosis. Interestingly, pretreatment with 3-MA and chloroquine remarkably suppressed CoCl2-induced caspase-3 activation and cell apoptosis. Application of p53 small interference (si)RNA into human U87-MG cells downregulated levels of this protein and simultaneously lowered hypoxiaand 3-MA-induced alterations in cell autophagy, apoptosis, and death. The hypoxia-induced autophagy and apoptosis of DBTRG-05MG cells were significantly lowered by 3-MA pretreatment and p53 knockdown. Therefore, the present study shows that CoCl2 treatment can induce autophagy of human glioma cells and subsequent autophagic apoptosis via a p53-dependent pathway. Hypoxia-induced autophagic apoptosis may be applied as a therapeutic strategy for treatment of glioma patients.",
keywords = "Autophagic Apoptosis, Autophagy, Hypoxia, Malignant Glioma, P53",
author = "Cheng, {Bor Chin} and Chen, {Jui Tai} and Yang, {Shun Tai} and Chio, {Chung Ching} and Liu, {Shing Hwa} and Chen, {Ruei Ming}",
year = "2017",
month = "3",
day = "1",
doi = "10.3892/ijo.2017.3861",
language = "English",
volume = "50",
pages = "964--974",
journal = "International Journal of Oncology",
issn = "1019-6439",
publisher = "Spandidos Publications",
number = "3",

}

TY - JOUR

T1 - Cobalt chloride treatment induces autophagic apoptosis in human glioma cells via a p53-dependent pathway

AU - Cheng, Bor Chin

AU - Chen, Jui Tai

AU - Yang, Shun Tai

AU - Chio, Chung Ching

AU - Liu, Shing Hwa

AU - Chen, Ruei Ming

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Malignant glioma is the most aggressive brain tumor. Hypoxic condition has been explored for killing cancer stem cells or drug-resistant tumor cells. This study investigated the effects of hypoxia on autophagic death and the possible mechanisms. Exposure of human malignant glioma U87-MG cells to cobalt chloride (CoCl2) increased cellular hypoxia-inducible factor-1α levels and concurrently decreased cell viability concentration-and time-dependently. In parallel, treatment with CoCl2 suppressed proliferation of human U87-MG cells. Autophagic cells and levels of LC3-II were concentration-and time-dependently induced in human U87-MG cells after exposure to CoCl2. However, pretreatment with 3-mehyladenine (3-MA) and chloroquine, inhibitors of cell autophagy, caused significant alleviations in CoCl2-induced cell autophagy. In contrast, exposure to rapamycin, an inducer of cell autophagy, synergistically induced hypoxiainduced autophagy of U87-MG cells. Administration of human U87-MG cells with CoCl2 triggered caspase-3 activation and cell apoptosis. Interestingly, pretreatment with 3-MA and chloroquine remarkably suppressed CoCl2-induced caspase-3 activation and cell apoptosis. Application of p53 small interference (si)RNA into human U87-MG cells downregulated levels of this protein and simultaneously lowered hypoxiaand 3-MA-induced alterations in cell autophagy, apoptosis, and death. The hypoxia-induced autophagy and apoptosis of DBTRG-05MG cells were significantly lowered by 3-MA pretreatment and p53 knockdown. Therefore, the present study shows that CoCl2 treatment can induce autophagy of human glioma cells and subsequent autophagic apoptosis via a p53-dependent pathway. Hypoxia-induced autophagic apoptosis may be applied as a therapeutic strategy for treatment of glioma patients.

AB - Malignant glioma is the most aggressive brain tumor. Hypoxic condition has been explored for killing cancer stem cells or drug-resistant tumor cells. This study investigated the effects of hypoxia on autophagic death and the possible mechanisms. Exposure of human malignant glioma U87-MG cells to cobalt chloride (CoCl2) increased cellular hypoxia-inducible factor-1α levels and concurrently decreased cell viability concentration-and time-dependently. In parallel, treatment with CoCl2 suppressed proliferation of human U87-MG cells. Autophagic cells and levels of LC3-II were concentration-and time-dependently induced in human U87-MG cells after exposure to CoCl2. However, pretreatment with 3-mehyladenine (3-MA) and chloroquine, inhibitors of cell autophagy, caused significant alleviations in CoCl2-induced cell autophagy. In contrast, exposure to rapamycin, an inducer of cell autophagy, synergistically induced hypoxiainduced autophagy of U87-MG cells. Administration of human U87-MG cells with CoCl2 triggered caspase-3 activation and cell apoptosis. Interestingly, pretreatment with 3-MA and chloroquine remarkably suppressed CoCl2-induced caspase-3 activation and cell apoptosis. Application of p53 small interference (si)RNA into human U87-MG cells downregulated levels of this protein and simultaneously lowered hypoxiaand 3-MA-induced alterations in cell autophagy, apoptosis, and death. The hypoxia-induced autophagy and apoptosis of DBTRG-05MG cells were significantly lowered by 3-MA pretreatment and p53 knockdown. Therefore, the present study shows that CoCl2 treatment can induce autophagy of human glioma cells and subsequent autophagic apoptosis via a p53-dependent pathway. Hypoxia-induced autophagic apoptosis may be applied as a therapeutic strategy for treatment of glioma patients.

KW - Autophagic Apoptosis

KW - Autophagy

KW - Hypoxia

KW - Malignant Glioma

KW - P53

UR - http://www.scopus.com/inward/record.url?scp=85013059734&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85013059734&partnerID=8YFLogxK

U2 - 10.3892/ijo.2017.3861

DO - 10.3892/ijo.2017.3861

M3 - Article

C2 - 28197638

AN - SCOPUS:85013059734

VL - 50

SP - 964

EP - 974

JO - International Journal of Oncology

JF - International Journal of Oncology

SN - 1019-6439

IS - 3

ER -