| Crosstalk between autophagy and apoptosis in the regulation of paclitaxel-induced cell death in v-Ha-ras-transformed fibroblasts. | |
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MedLine Citation:
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PMID: 21069434 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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The previous studies by this author group has shown that paclitaxel, a mitotic inhibitor used in breast cancer chemotherapy, inhibits cell growth via induction of Raf-1-dependent apoptosis. In this article, the role of autophagy in paclitaxel anticancer action was investigated using v-Ha-ras-transformed NIH 3T3 cells. Paclitaxel induced a notable increase in the number of fluorescent particles labeled with monodansylcadaverine (MDC), a specific marker for autophagic vacuoles. MDC-labeled vacuoles clearly exhibited the fluorescent-tagged LC3 in cells transiently overexpressing GFP-LC3 (a protein that associates with autophagosome membranes). However, autophagy inhibition with 3-methyladenine (3-MA) failed to rescue v-Ha-ras-transformed NIH 3T3 cells from paclitaxel-induced cell death. More interestingly, the apoptosis inhibition by overexpression of the X-linked inhibitor of apoptosis (XIAP) did not fully block the cell death by paclitaxel, implying that apoptosis inhibition might accelerate the autophagic components of the paclitaxel response. Conversely, Raf-1 shRNA expression protected against paclitaxel-induced cell death through the simultaneous inhibition of both autophagy and apoptosis. These results suggest that both autophagy and apoptosis act as cooperative partners to induce cell death in v-Ha-ras-transformed NIH 3T3 cells treated with paclitaxel. |
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Authors:
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Ki-Hwan Eum; Michael Lee |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-11 |
Journal Detail:
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Title: Molecular and cellular biochemistry Volume: 348 ISSN: 1573-4919 ISO Abbreviation: Mol. Cell. Biochem. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-06 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0364456 Medline TA: Mol Cell Biochem Country: Netherlands |
Other Details:
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Languages: eng Pagination: 61-8 Citation Subset: IM |
Affiliation:
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Division of Life Sciences, College of Natural Sciences, University of Incheon, Yeonsu-gu, Incheon, Republic of Korea. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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