Thioridazine, an antipsychotic agent, inhibits cancer stem cell growth and induces autophagy of Glioblastoma Multiforme
碩士 === 國立陽明大學 === 生物藥學研究所 === 102 === Glioblastoma multiforme (GBM) is a highly aggressive brain tumor characterized by increased proliferation and resistance to chemotherapy and radiotherapy. Glioblastoma stem cells (GSCs) have been proposed to be involved in tumorigenesis, tumor maintenance and th...
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ndltd-TW-102YM0056030042015-10-13T23:50:23Z http://ndltd.ncl.edu.tw/handle/03732371190588805985 Thioridazine, an antipsychotic agent, inhibits cancer stem cell growth and induces autophagy of Glioblastoma Multiforme 抗精神疾病用藥(Thioridazine) 抑制多形性膠質細胞瘤幹細胞的生長及誘導細胞自嗜作用 Hui-Wen Cheng 鄭惠文 碩士 國立陽明大學 生物藥學研究所 102 Glioblastoma multiforme (GBM) is a highly aggressive brain tumor characterized by increased proliferation and resistance to chemotherapy and radiotherapy. Glioblastoma stem cells (GSCs) have been proposed to be involved in tumorigenesis, tumor maintenance and therapeutic resistance. Currently, temozolomide is the only FDA-approved treatment for GBM. Therefore, there is an urgent need to discover novel candidate therapeutic drugs for GBM. Here, we identified thioridazine, an anti-psychotic drug, as a potential treatment for GBM via the Connectivity Map database. Thioridazine can cross the blood-brain barrier (BBB), providing a significant advantage over current drug delivery limitations. We demonstrate that thioridazine inhibits the cell viability of both GBM cells and GSCs. Thioridazine induces autophagy in GBM cells and GSCs, as evident by the up-regulation of LC3II, and up-regulates AMPK activity. Moreover, thioridazine induces ER stress in GBM cells. Finally, thioridazine suppresses GBM tumorigenesis and induces autophagy in vivo. The data suggest that thioridazine-induced autophagy has an anti-cancer effect in GBM through activation of AMPK. In summary, we repurpose the anti-psychotic drug, thioridazine, as a potent anti-GBM and anti-GBM cancer stem cell agent for potential clinical trial in the future. Chi-Ying F. Huang 黃奇英 2014 學位論文 ; thesis 72 en_US |
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碩士 === 國立陽明大學 === 生物藥學研究所 === 102 === Glioblastoma multiforme (GBM) is a highly aggressive brain tumor characterized by increased proliferation and resistance to chemotherapy and radiotherapy. Glioblastoma stem cells (GSCs) have been proposed to be involved in tumorigenesis, tumor maintenance and therapeutic resistance. Currently, temozolomide is the only FDA-approved treatment for GBM. Therefore, there is an urgent need to discover novel candidate therapeutic drugs for GBM. Here, we identified thioridazine, an anti-psychotic drug, as a potential treatment for GBM via the Connectivity Map database. Thioridazine can cross the blood-brain barrier (BBB), providing a significant advantage over current drug delivery limitations. We demonstrate that thioridazine inhibits the cell viability of both GBM cells and GSCs. Thioridazine induces autophagy in GBM cells and GSCs, as evident by the up-regulation of LC3II, and up-regulates AMPK activity. Moreover, thioridazine induces ER stress in GBM cells. Finally, thioridazine suppresses GBM tumorigenesis and induces autophagy in vivo. The data suggest that thioridazine-induced autophagy has an anti-cancer effect in GBM through activation of AMPK. In summary, we repurpose the anti-psychotic drug, thioridazine, as a potent anti-GBM and anti-GBM cancer stem cell agent for potential clinical trial in the future.
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author2 |
Chi-Ying F. Huang |
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Chi-Ying F. Huang Hui-Wen Cheng 鄭惠文 |
author |
Hui-Wen Cheng 鄭惠文 |
spellingShingle |
Hui-Wen Cheng 鄭惠文 Thioridazine, an antipsychotic agent, inhibits cancer stem cell growth and induces autophagy of Glioblastoma Multiforme |
author_sort |
Hui-Wen Cheng |
title |
Thioridazine, an antipsychotic agent, inhibits cancer stem cell growth and induces autophagy of Glioblastoma Multiforme |
title_short |
Thioridazine, an antipsychotic agent, inhibits cancer stem cell growth and induces autophagy of Glioblastoma Multiforme |
title_full |
Thioridazine, an antipsychotic agent, inhibits cancer stem cell growth and induces autophagy of Glioblastoma Multiforme |
title_fullStr |
Thioridazine, an antipsychotic agent, inhibits cancer stem cell growth and induces autophagy of Glioblastoma Multiforme |
title_full_unstemmed |
Thioridazine, an antipsychotic agent, inhibits cancer stem cell growth and induces autophagy of Glioblastoma Multiforme |
title_sort |
thioridazine, an antipsychotic agent, inhibits cancer stem cell growth and induces autophagy of glioblastoma multiforme |
publishDate |
2014 |
url |
http://ndltd.ncl.edu.tw/handle/03732371190588805985 |
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