Combination of Rad001 (Everolimus) and Propachlor Synergistically Induces Apoptosis through Enhanced Autophagy in Prostate Cancer Cells
| Autor: | Nan Liu, Yin Sun, Chaozhao Liang, Ryan K. Thor, Elaine Hsia, Robert Damoiseaux, Boxiao Ding, Sheng Tai, Sunita Bhuta, Jiaoti Huang |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Cancer Research Programmed cell death Antineoplastic Agents Apoptosis Mice SCID Biology Pharmacology medicine.disease_cause Article Autophagy-Related Protein 5 Mice Prostate cancer Cell Line Tumor Autophagy medicine Animals Humans Everolimus Protein kinase B PI3K/AKT/mTOR pathway Sirolimus Membrane Proteins Prostatic Neoplasms Drug Synergism medicine.disease Oncology Small Ubiquitin-Related Modifier Proteins Acetanilides Beclin-1 Apoptosis Regulatory Proteins Carcinogenesis Microtubule-Associated Proteins Autophagy-Related Protein 12 medicine.drug |
| Zdroj: | Molecular Cancer Therapeutics. 11:1320-1331 |
| ISSN: | 1538-8514 1535-7163 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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