Effects of Chloroquine on Lysosomal and Mitochondrial Activities and Cell Death of Leukemia Cells
碩士 === 慈濟大學 === 醫學生物技術碩士班 === 105 === The two main routes of cellular protein degradation are mediated via the lysosome and the proteasome. The proteasome system is evident to be a promising anticancer target. However, the significance of lysosomes in cancer therapy has not been well elucidated...
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ndltd-TW-105TCU006040062019-05-15T23:31:51Z http://ndltd.ncl.edu.tw/handle/y6tm7u Effects of Chloroquine on Lysosomal and Mitochondrial Activities and Cell Death of Leukemia Cells Chloroquine對血癌細胞溶小體及粒線體活性與細胞存亡的影響 HUANG, LI-YUN 黃莉云 碩士 慈濟大學 醫學生物技術碩士班 105 The two main routes of cellular protein degradation are mediated via the lysosome and the proteasome. The proteasome system is evident to be a promising anticancer target. However, the significance of lysosomes in cancer therapy has not been well elucidated. The lysosomal machinery functions effectively only in acidic environment. Chronic myelogenous leukemia (CML) stem cells induces autophagy as a survival mechanism in tyrosine kinase inhibitor treatment. In this study, we assessed the effect of chloroquine (CQ)-disrupted lysosomal acidification on mitochondrial activity in human leukemia K562 cells. After staining of specific fluorescent dyes, we detected various cellular activities by flowcytometry. Our results showed that treatment with higher doses of CQ decreased both the cellular viability and acidic vesicular organelles, but increased mitochondrial mass and mitochondrial activity. Although CQ will become protonated that decrease cellular H+ concentration, but our results showed that it just affect intravesicular pH (pHv), but not intracellular pH (pHi). And ETC complex I inhibitor could enhance CQ-induced K562 cell death, ROS and ETC complex V inhibitors could promote resistance of K562 cell to CQ. However, the intracellular calcium did not play a role in CQ treated cells. Overall, CQ not only affect the function of lysosome, but mitochondria. And CQ induces type III programmed cell death, necroptosis in K562 cells. SU, SHU-HUI 蘇淑惠 2017 學位論文 ; thesis 62 zh-TW |
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碩士 === 慈濟大學 === 醫學生物技術碩士班 === 105 === The two main routes of cellular protein degradation are mediated via the lysosome and the proteasome. The proteasome system is evident to be a promising anticancer target. However, the significance of lysosomes in cancer therapy has not been well elucidated. The lysosomal machinery functions effectively only in acidic environment. Chronic myelogenous leukemia (CML) stem cells induces autophagy as a survival mechanism in tyrosine kinase inhibitor treatment. In this study, we assessed the effect of chloroquine (CQ)-disrupted lysosomal acidification on mitochondrial activity in human leukemia K562 cells.
After staining of specific fluorescent dyes, we detected various cellular activities by flowcytometry. Our results showed that treatment with higher doses of CQ decreased both the cellular viability and acidic vesicular organelles, but increased mitochondrial mass and mitochondrial activity. Although CQ will become protonated that decrease cellular H+ concentration, but our results showed that it just affect intravesicular pH (pHv), but not intracellular pH (pHi). And ETC complex I inhibitor could enhance CQ-induced K562 cell death, ROS and ETC complex V inhibitors could promote resistance of K562 cell to CQ. However, the intracellular calcium did not play a role in CQ treated cells. Overall, CQ not only affect the function of lysosome, but mitochondria. And CQ induces type III programmed cell death, necroptosis in K562 cells.
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author2 |
SU, SHU-HUI |
author_facet |
SU, SHU-HUI HUANG, LI-YUN 黃莉云 |
author |
HUANG, LI-YUN 黃莉云 |
spellingShingle |
HUANG, LI-YUN 黃莉云 Effects of Chloroquine on Lysosomal and Mitochondrial Activities and Cell Death of Leukemia Cells |
author_sort |
HUANG, LI-YUN |
title |
Effects of Chloroquine on Lysosomal and Mitochondrial Activities and Cell Death of Leukemia Cells |
title_short |
Effects of Chloroquine on Lysosomal and Mitochondrial Activities and Cell Death of Leukemia Cells |
title_full |
Effects of Chloroquine on Lysosomal and Mitochondrial Activities and Cell Death of Leukemia Cells |
title_fullStr |
Effects of Chloroquine on Lysosomal and Mitochondrial Activities and Cell Death of Leukemia Cells |
title_full_unstemmed |
Effects of Chloroquine on Lysosomal and Mitochondrial Activities and Cell Death of Leukemia Cells |
title_sort |
effects of chloroquine on lysosomal and mitochondrial activities and cell death of leukemia cells |
publishDate |
2017 |
url |
http://ndltd.ncl.edu.tw/handle/y6tm7u |
work_keys_str_mv |
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