| Effect of Costunolide and Dehydrocostus Lactone on Cell Cycle, Apoptosis, and ABC Transporter Expression in Human Soft Tissue Sarcoma Cells. | |
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MedLine Citation:
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PMID: 23047249 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Human soft tissue sarcomas represent a rare group of malignant tumours that frequently exhibit chemotherapeutic resistance and increased metastatic potential following unsuccessful treatment. In this study, we investigated the effects of costunolide and dehydrocostus lactone, which have been isolated from Saussurea lappa using activity-guided isolation, on three soft tissue sarcoma cell lines of various origins. The effects on cell proliferation, cell cycle distribution, apoptosis induction, and ABC transporter expression were analysed.Both compounds inhibited cell viability dose- and time-dependently. IC50 values ranged from 6.2 µg/mL to 9.8 µg/mL. Cells treated with costunolide showed no changes in cell cycle, little in caspase 3/7 activity, and low levels of cleaved caspase-3 after 24 and 48 h. Dehydrocostus lactone caused a significant reduction of cells in the G1 phase and an increase of cells in the S and G2/M phase. Moreover, it led to enhanced caspase 3/7 activity, cleaved caspase-3, and cleaved PARP indicating apoptosis induction. In addition, the influence of costunolide and dehydrocostus lactone on the expression of ATP binding cassette transporters related to multidrug resistance (ABCB1/MDR1, ABCC1/MRP1, and ABCG2/BCRP1) was examined using real-time RT-PCR. The expressions of ABCB1/MDR1 and ABCG2/BCRP1 in liposarcoma and synovial sarcoma cells were significantly downregulated by dehydrocostus lactone.Our data demonstrate for the first time that dehydrocostus lactone affects cell viability, cell cycle distribution and ABC transporter expression in soft tissue sarcoma cell lines. Furthermore, it led to caspase 3/7 activity as well as caspase-3 and PARP cleavage, which are indicators of apoptosis. Therefore, this compound may be a promising lead candidate for the development of therapeutic agents against drug-resistant tumours. |
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Authors:
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Nadine Kretschmer; Beate Rinner; Nicole Stuendl; Heike Kaltenegger; Elisabeth Wolf; Olaf Kunert; Herbert Boechzelt; Andreas Leithner; Rudolf Bauer; Birgit Lohberger |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-10-9 |
Journal Detail:
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Title: Planta medica Volume: - ISSN: 1439-0221 ISO Abbreviation: Planta Med. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0066751 Medline TA: Planta Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Georg Thieme Verlag KG Stuttgart · New York. |
Affiliation:
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Institute of Pharmaceutical Sciences, Department of Pharmacognosy, Karl-Franzens-University, Graz, Austria. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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