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Combination of Rad001 (everolimus) and propachlor synergistically induces apoptosis through enhanced autophagy in prostate cancer cells.

Publication ,  Journal Article
Tai, S; Sun, Y; Liu, N; Ding, B; Hsia, E; Bhuta, S; Thor, RK; Damoiseaux, R; Liang, C; Huang, J
Published in: Mol Cancer Ther
June 2012

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.

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Published In

Mol Cancer Ther

DOI

EISSN

1538-8514

Publication Date

June 2012

Volume

11

Issue

6

Start / End Page

1320 / 1331

Location

United States

Related Subject Headings

  • Small Ubiquitin-Related Modifier Proteins
  • Sirolimus
  • Prostatic Neoplasms
  • Oncology & Carcinogenesis
  • Microtubule-Associated Proteins
  • Mice, SCID
  • Mice
  • Membrane Proteins
  • Male
  • Humans
 

Citation

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Tai, S., Sun, Y., Liu, N., Ding, B., Hsia, E., Bhuta, S., … Huang, J. (2012). Combination of Rad001 (everolimus) and propachlor synergistically induces apoptosis through enhanced autophagy in prostate cancer cells. Mol Cancer Ther, 11(6), 1320–1331. https://doi.org/10.1158/1535-7163.MCT-11-0954
Tai, Sheng, Yin Sun, Nan Liu, Boxiao Ding, Elaine Hsia, Sunita Bhuta, Ryan K. Thor, Robert Damoiseaux, Chaozhao Liang, and Jiaoti Huang. “Combination of Rad001 (everolimus) and propachlor synergistically induces apoptosis through enhanced autophagy in prostate cancer cells.Mol Cancer Ther 11, no. 6 (June 2012): 1320–31. https://doi.org/10.1158/1535-7163.MCT-11-0954.
Tai S, Sun Y, Liu N, Ding B, Hsia E, Bhuta S, et al. Combination of Rad001 (everolimus) and propachlor synergistically induces apoptosis through enhanced autophagy in prostate cancer cells. Mol Cancer Ther. 2012 Jun;11(6):1320–31.
Tai, Sheng, et al. “Combination of Rad001 (everolimus) and propachlor synergistically induces apoptosis through enhanced autophagy in prostate cancer cells.Mol Cancer Ther, vol. 11, no. 6, June 2012, pp. 1320–31. Pubmed, doi:10.1158/1535-7163.MCT-11-0954.
Tai S, Sun Y, Liu N, Ding B, Hsia E, Bhuta S, Thor RK, Damoiseaux R, Liang C, Huang J. Combination of Rad001 (everolimus) and propachlor synergistically induces apoptosis through enhanced autophagy in prostate cancer cells. Mol Cancer Ther. 2012 Jun;11(6):1320–1331.

Published In

Mol Cancer Ther

DOI

EISSN

1538-8514

Publication Date

June 2012

Volume

11

Issue

6

Start / End Page

1320 / 1331

Location

United States

Related Subject Headings

  • Small Ubiquitin-Related Modifier Proteins
  • Sirolimus
  • Prostatic Neoplasms
  • Oncology & Carcinogenesis
  • Microtubule-Associated Proteins
  • Mice, SCID
  • Mice
  • Membrane Proteins
  • Male
  • Humans