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Molecular Cancer Therapeutics
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Therapeutic Discovery

Combination of Rad001 (Everolimus) and Propachlor Synergistically Induces Apoptosis through Enhanced Autophagy in Prostate Cancer Cells

Sheng Tai, Yin Sun, Nan Liu, Boxiao Ding, Elaine Hsia, Sunita Bhuta, Ryan K. Thor, Robert Damoiseaux, Chaozhao Liang and Jiaoti Huang
Sheng Tai
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Yin Sun
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Nan Liu
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Boxiao Ding
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Elaine Hsia
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Sunita Bhuta
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Ryan K. Thor
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Robert Damoiseaux
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Chaozhao Liang
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Jiaoti Huang
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DOI: 10.1158/1535-7163.MCT-11-0954 Published June 2012
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Abstract

PI3K/AKT/mTOR pathway plays a key role in the tumorigenesis of many human cancers including prostate cancer. However, inhibitors of this pathway, such as Rad001, have not shown therapeutic efficacy as a single agent. Through a high-throughput screen of 5,000 widely used small molecules, we identified compounds that can synergize with Rad001 to inhibit prostate cancer cells. One of the compounds, propachlor, synergizes with Rad001 to induce apoptosis of castration-resistant prostate cancer cells via enhanced autophagy. This enhanced autophagic cell death is accompanied by increased Beclin1 expression as well as upregulation of Atg5–Atg12 conjugate and LC3-2. Rad001 and propachlor can also synergistically inhibit tumors in a xenograft animal model of prostate cancer. These findings provide a novel direction to develop combination therapies for advanced and metastatic prostate cancer that has failed the currently available therapies. Mol Cancer Ther; 11(6); 1320–31. ©2012 AACR.

  • Received November 23, 2011.
  • Revision received March 13, 2012.
  • Accepted March 28, 2012.
  • ©2012 American Association for Cancer Research.
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Molecular Cancer Therapeutics: 11 (6)
June 2012
Volume 11, Issue 6
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Combination of Rad001 (Everolimus) and Propachlor Synergistically Induces Apoptosis through Enhanced Autophagy in Prostate Cancer Cells
Sheng Tai, Yin Sun, Nan Liu, Boxiao Ding, Elaine Hsia, Sunita Bhuta, Ryan K. Thor, Robert Damoiseaux, Chaozhao Liang and Jiaoti Huang
Mol Cancer Ther June 1 2012 (11) (6) 1320-1331; DOI: 10.1158/1535-7163.MCT-11-0954

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Combination of Rad001 (Everolimus) and Propachlor Synergistically Induces Apoptosis through Enhanced Autophagy in Prostate Cancer Cells
Sheng Tai, Yin Sun, Nan Liu, Boxiao Ding, Elaine Hsia, Sunita Bhuta, Ryan K. Thor, Robert Damoiseaux, Chaozhao Liang and Jiaoti Huang
Mol Cancer Ther June 1 2012 (11) (6) 1320-1331; DOI: 10.1158/1535-7163.MCT-11-0954
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Molecular Cancer Therapeutics
eISSN: 1538-8514
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