| Dihydroptychantol A, a macrocyclic bisbibenzyl derivative, induces autophagy and following apoptosis associated with p53 pathway in human osteosarcoma U2OS cells. | |
MedLine Citation:
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PMID: 21185854 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Dihydroptychantol A (DHA), a novel macrocyclic bisbibenzyl compound extracted from liverwort Asterella angusta, has antifungal and multi-drug resistance reversal properties. Here, the chemically synthesized DHA was employed to test its anti-cancer activities in human osteosarcoma U2OS cells. Our results demonstrated that DHA induced autophagy followed by apoptotic cell death accompanied with G(2)/M-phase cell cycle arrest in U2OS cells. DHA-induced autophagy was morphologically characterized by the formation of double membrane-bound autophagic vacuoles recognizable at the ultrastructural level. DHA also increased the levels of LC3-II, a marker of autophagy. Surprisingly, DHA-mediated apoptotic cell death was potentiated by the autophagy inhibitor 3-methyladenine, suggesting that autophagy may play a protective role that impedes the eventual cell death. Furthermore, p53 was shown to be involved in DHA-meditated autophagy and apoptosis. In this connection, DHA increased nuclear expression of p53, induced p53 phosphorylation, and upregulated p53 target gene p21(Waf1/Cip1). In contrast, cytoplasmic p53 was reduced by DHA, which contributed to the stimulation of autophagy. In relation to the cell cycle, DHA decreased the expression of cyclin B(1), a cyclin required for progression through the G(2)/M phase. Taken together, DHA induces G(2)/M-phase cell cycle arrest and apoptosis in U2OS cells. DHA-induced apoptosis was preceded by the induction of protective autophagy. DHA-mediated autophagy and apoptosis are associated with the cytoplasmic and nuclear functions of p53. |
Authors:
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Xia Li; William K K Wu; Bin Sun; Min Cui; Shanshan Liu; Jian Gao; Hongxiang Lou |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2010-12-24 |
Journal Detail:
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Title: Toxicology and applied pharmacology Volume: - ISSN: 1096-0333 ISO Abbreviation: - Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2011-1-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0416575 Medline TA: Toxicol Appl Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China; School of Ocean, Shandong University, Weihai 264209, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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