| Hyperthermia-enhanced TRAIL- and mapatumumab-induced apoptotic death is mediated through mitochondria in human colon cancer cells. | |
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MedLine Citation:
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PMID: 22174016 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Colorectal cancer is the third leading cause of cancer-related mortality in the world; death usually results from uncontrolled metastatic disease. Previously, we developed a novel strategy of TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) in combination with hyperthermia to treat hepatic colorectal metastases. However, previous studies suggest a potential hepatocyte cytotoxicity with TRAIL. Unlike TRAIL, anti-human TRAIL receptor antibody induces apoptosis without hepatocyte toxicity. In this study, we evaluated the anti-tumor efficacy of humanized anti-death receptor 4 (DR4) antibody mapatumumab (Mapa) by comparing it with TRAIL in combination with hyperthermia. TRAIL, which binds to both DR4 and death receptor 5 (DR5), was approximately 10-fold more effective than Mapa in inducing apoptosis. However, hyperthermia enhances apoptosis induced by either agent. We observed that the synergistic effect was mediated through elevation of reactive oxygen species, c-Jun N-terminal kinase activation, Bax oligomerization and translocalization to the mitochondria, loss of mitochondrial membrane potential, release of cytochrome c to cytosol, activation of caspases and increase in poly(ADP-ribose) polymerase cleavage. We believe that the successful outcome of this study will support the application of Mapa in combination with hyperthermia to colorectal hepatic metastases. J. Cell. Biochem. © 2011 Wiley Periodicals, Inc. |
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Authors:
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Xinxin Song; Han-Cheon Kim; Seog-Young Kim; Per Basse; Bae-Hang Park; Byeong-Chel Lee; Yong J Lee |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-15 |
Journal Detail:
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Title: Journal of cellular biochemistry Volume: - ISSN: 1097-4644 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8205768 Medline TA: J Cell Biochem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Wiley Periodicals, Inc. |
Affiliation:
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Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA; University of Pittsburgh Cancer Institute, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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