TAK1 inhibitor 5Z-7-oxozeaenol sensitizes cervical cancer to doxorubicin-induced apoptosis

Aberrant activation of nuclear factor-κB (NF-κB) allows cancer cells to escape chemotherapy-induced cell death and acts as one of the major mechanisms of acquired chemoresistance in cervical cancer. TAK1, a crucial mediator that upregulates NF-κB activation in response to cellular genotoxic stress,...

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Published in:Oncotarget 2017-05, Vol.8 (20), p.33666-33675
Main Authors: Guan, Shan, Lu, Jiaxiong, Zhao, Yanling, Woodfield, Sarah E, Zhang, Huiyuan, Xu, Xin, Yu, Yang, Zhao, Jing, Bieerkehazhi, Shayahati, Liang, Haoqian, Yang, Jianhua, Zhang, Fuchun, Sun, Surong
Format: Article
Language:English
Subjects:
Antibiotics, Antineoplastic - pharmacology
Apoptosis - drug effects
Cell Line, Tumor
Cell Proliferation - drug effects
Cell Survival - drug effects
Doxorubicin - pharmacology
Drug Synergism
Female
Humans
MAP Kinase Kinase Kinases - antagonists & inhibitors
MAP Kinase Signaling System - drug effects
NF-kappa B - metabolism
Research Paper
Signal Transduction - drug effects
Uterine Cervical Neoplasms - metabolism
Zearalenone - analogs & derivatives
Zearalenone - pharmacology
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Summary:Aberrant activation of nuclear factor-κB (NF-κB) allows cancer cells to escape chemotherapy-induced cell death and acts as one of the major mechanisms of acquired chemoresistance in cervical cancer. TAK1, a crucial mediator that upregulates NF-κB activation in response to cellular genotoxic stress, is required for tumor cell viability and survival. Herein, we examined whether TAK1 inhibition is a potential therapeutic strategy for treating cervical cancer. We found that TAK1 inhibitor 5Z-7-oxozeaenol significantly augmented the cytotoxic effects of Dox in a panel of cervical cancer cell lines. Treatment with 5Z-7-oxozeaenol hindered Dox-induced NF-κB activation and promoted Dox-induced apoptosis in cervical cancer cells. Moreover, 5Z-7-oxozeaenol showed similar effects in both positive and negative human papillomavirus-infected cervical cancer cells. Taken together, our results provide evidence that TAK1 inhibition significantly sensitizes cervical cancer cells to chemotherapy-induced cell death and supports the use of TAK1 inhibitor with current chemotherapies in the clinic for patients with refractory cervical cancer.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.16895