BET inhibitor I-BET151 sensitizes GBM cells to temozolomide via PUMA induction

Zhicheng Yao; Shida Yang; Hongyou Zhao; Huike Yang; Xin Jiang

doi:10.1038/s41417-018-0068-4

BET inhibitor I-BET151 sensitizes GBM cells to temozolomide via PUMA induction

Zhicheng Yao, Shida Yang, Hongyou Zhao, Huike Yang, Xin Jiang^*

^*Corresponding author for this work

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

9 Citations (Scopus)

Abstract

A significant roadblock in treatment of GBM multiforme (GBM) isresistance to temozolomide (TMZ). In this study, we investigated whether I-BET151, aspecific BET inhibitor, could sensitize GBM cells to TMZ. Our findings showed thatthe action of I-BET151 could augment the effect of TMZ on cancer cells U251 and U87cells. In U251 cells, administration of I-BET151 increased the TMZ-induced apoptosisGBM cells. I-BET151 remarkably enhanced the activities of caspase-3. In addition,I-BET151 promoted TMZ-induced migration and invasion in GBM cells. Moreover,I-BET151 increased the amount of reactive oxygen species as well as superoxideanions with a decrease of activity of SOD and the anti-oxidative properties of GBMcells. I-BET151 also induced increased PUMA expression, which is required for thefunctions of I-BET151 and regulates the synergistic cytotoxic effects of i-BET151and TMZ in GBM cells. I-BET151 with TMZ also showed synergistic cytotoxic effects invivo. These point out to an approach to tackle GBM using TMZ along with BETinhibitors.

Original language	English
Pages (from-to)	226-234
Number of pages	9
Journal	Cancer Gene Therapy
Volume	27
Issue number	3-4
DOIs	https://doi.org/10.1038/s41417-018-0068-4
Publication status	Published - 1 Apr 2020
Externally published	Yes

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title = "BET inhibitor I-BET151 sensitizes GBM cells to temozolomide via PUMA induction",

abstract = "A significant roadblock in treatment of GBM multiforme (GBM) isresistance to temozolomide (TMZ). In this study, we investigated whether I-BET151, aspecific BET inhibitor, could sensitize GBM cells to TMZ. Our findings showed thatthe action of I-BET151 could augment the effect of TMZ on cancer cells U251 and U87cells. In U251 cells, administration of I-BET151 increased the TMZ-induced apoptosisGBM cells. I-BET151 remarkably enhanced the activities of caspase-3. In addition,I-BET151 promoted TMZ-induced migration and invasion in GBM cells. Moreover,I-BET151 increased the amount of reactive oxygen species as well as superoxideanions with a decrease of activity of SOD and the anti-oxidative properties of GBMcells. I-BET151 also induced increased PUMA expression, which is required for thefunctions of I-BET151 and regulates the synergistic cytotoxic effects of i-BET151and TMZ in GBM cells. I-BET151 with TMZ also showed synergistic cytotoxic effects invivo. These point out to an approach to tackle GBM using TMZ along with BETinhibitors.",

author = "Zhicheng Yao and Shida Yang and Hongyou Zhao and Huike Yang and Xin Jiang",

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doi = "10.1038/s41417-018-0068-4",

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T1 - BET inhibitor I-BET151 sensitizes GBM cells to temozolomide via PUMA induction

AU - Yao, Zhicheng

AU - Yang, Shida

AU - Zhao, Hongyou

AU - Yang, Huike

AU - Jiang, Xin

PY - 2020/4/1

Y1 - 2020/4/1

N2 - A significant roadblock in treatment of GBM multiforme (GBM) isresistance to temozolomide (TMZ). In this study, we investigated whether I-BET151, aspecific BET inhibitor, could sensitize GBM cells to TMZ. Our findings showed thatthe action of I-BET151 could augment the effect of TMZ on cancer cells U251 and U87cells. In U251 cells, administration of I-BET151 increased the TMZ-induced apoptosisGBM cells. I-BET151 remarkably enhanced the activities of caspase-3. In addition,I-BET151 promoted TMZ-induced migration and invasion in GBM cells. Moreover,I-BET151 increased the amount of reactive oxygen species as well as superoxideanions with a decrease of activity of SOD and the anti-oxidative properties of GBMcells. I-BET151 also induced increased PUMA expression, which is required for thefunctions of I-BET151 and regulates the synergistic cytotoxic effects of i-BET151and TMZ in GBM cells. I-BET151 with TMZ also showed synergistic cytotoxic effects invivo. These point out to an approach to tackle GBM using TMZ along with BETinhibitors.

AB - A significant roadblock in treatment of GBM multiforme (GBM) isresistance to temozolomide (TMZ). In this study, we investigated whether I-BET151, aspecific BET inhibitor, could sensitize GBM cells to TMZ. Our findings showed thatthe action of I-BET151 could augment the effect of TMZ on cancer cells U251 and U87cells. In U251 cells, administration of I-BET151 increased the TMZ-induced apoptosisGBM cells. I-BET151 remarkably enhanced the activities of caspase-3. In addition,I-BET151 promoted TMZ-induced migration and invasion in GBM cells. Moreover,I-BET151 increased the amount of reactive oxygen species as well as superoxideanions with a decrease of activity of SOD and the anti-oxidative properties of GBMcells. I-BET151 also induced increased PUMA expression, which is required for thefunctions of I-BET151 and regulates the synergistic cytotoxic effects of i-BET151and TMZ in GBM cells. I-BET151 with TMZ also showed synergistic cytotoxic effects invivo. These point out to an approach to tackle GBM using TMZ along with BETinhibitors.

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SN - 0929-1903

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EP - 234

JO - Cancer Gene Therapy

JF - Cancer Gene Therapy

IS - 3-4

ER -

BET inhibitor I-BET151 sensitizes GBM cells to temozolomide via PUMA induction

Abstract

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