Oncotarget

Research Papers:

YM155, a survivin suppressant, triggers PARP-dependent cell death (parthanatos) and inhibits esophageal squamous-cell carcinoma xenografts in mice

Nan Zhao _, Yousheng Mao, Gaijing Han, Qiang Ju, Lanping Zhou, Fang Liu, Yang Xu and Xiaohang Zhao

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Oncotarget. 2015; 6:18445-18459. https://doi.org/10.18632/oncotarget.4315

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Abstract

Nan Zhao1,*, Yousheng Mao2,*, Gaijing Han1, Qiang Ju1, Lanping Zhou1, Fang Liu1, Yang Xu1, Xiaohang Zhao1

1State Key Laboratory of Molecular Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

2Department of Thoracic Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

*These authors have contributed equally to this work

Correspondence to:

Yang Xu, e-mail: xuyang@cicams.ac.cn

Xiaohang Zhao, e-mail: zhaoxh@cicams.ac.cn

Keywords: PARP, parthanatos, chemotherapy, esophageal cancer

Received: March 12, 2015     Accepted: June 02, 2015     Published: June 15, 2015

ABSTRACT

Here we demonstrated that sepantronium bromide (YM155), a survivin suppressant, inhibited esophageal squamous-cell carcinoma (ESCC) growth in mice bearing human ESCC xenografts without affecting body weight. In cell culture, YM155 decreased survivin levels and caused PARP-1 activation, poly-ADP polymer formation, and AIF translocation from the cytosol to the nucleus. Genetic knockdown of PARP-1 or AIF abrogated YM155-induced parthanatos cell death. Furthermore, FOS, JUN and c-MYC gene transcription, which is stimulated by activated PARP-1, was increased following YM155 treatment. Our data demonstrate that YM155 did not trigger apoptosis, but induced parthanatos, a cell death dependent on PARP-1 hyper-activation, and support clinical development of YM155 in ESCC.


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