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TAK1 Inhibitor 5Z-7-oxozeaenol Sensitizes Cervical Cancer to Doxorubicin-Induced Apoptosis

TAK1 Inhibitor 5Z-7-oxozeaenol Sensitizes Cervical Cancer to Doxorubicin-Induced Apoptosis

Shan Guan, Jiaxiong Lu, Yanling Zhao, Sarah E Woodfield, Huiyuan Zhang, Xin Xu, Yang Yu, Jing Zhao, Shayahati Bieerkehazhi, Haoqian Liang, Jianhua Yang, Fuchun Zhang, Surong Sun

Oncotarget. 2017 May 16;8(20):33666-33675.

PMID: 28430599

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP253863193	5Z-7-Oxozeaenol		253863-19-3	Price

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