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Kretschmer, N; Rinner, B; Stuendl, N; Kaltenegger, H; Wolf, E; Kunert, O; Boechzelt, H; Leithner, A; Bauer, R; Lohberger, B.
Effect of costunolide and dehydrocostus lactone on cell cycle, apoptosis, and ABC transporter expression in human soft tissue sarcoma cells.
Planta Med. 2012; 78(16):1749-1756 [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Eck Nicole
Kaltenegger Heike
Kretschmer Nadine
Leithner Andreas
Lohberger Birgit
Rinner Beate
Wolf Elisabeth

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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. Georg Thieme Verlag KG Stuttgart · New York.
Find related publications in this database (using NLM MeSH Indexing)
ATP Binding Cassette Transporter, Subfamily B -
ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics
ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism
ATP Binding Cassette Transporter, Subfamily G, Member 2 -
ATP-Binding Cassette Transporters - genetics
ATP-Binding Cassette Transporters - metabolism
Antineoplastic Agents, Phytogenic - chemistry
Antineoplastic Agents, Phytogenic - isolation & purification
Antineoplastic Agents, Phytogenic - pharmacology
Apoptosis - drug effects
Blotting, Western -
Caspase 3 - metabolism
Caspase 7 - metabolism
Cell Cycle - drug effects
Cell Proliferation - drug effects
Cell Survival -
Dose-Response Relationship, Drug -
Drug Screening Assays, Antitumor -
Enzyme Activation - drug effects
Gene Expression Regulation, Neoplastic -
Humans -
Inhibitory Concentration 50 -
Lactones - chemistry
Lactones - isolation & purification
Lactones - pharmacology
Multidrug Resistance-Associated Proteins - genetics
Multidrug Resistance-Associated Proteins - metabolism
Neoplasm Proteins - genetics
Neoplasm Proteins - metabolism
Proteolysis -
Real-Time Polymerase Chain Reaction -
Sarcoma - genetics
Sarcoma - pathology
Saussurea - chemistry
Sesquiterpenes - chemistry
Sesquiterpenes - isolation & purification
Sesquiterpenes - pharmacology
Time Factors -

Find related publications in this database (Keywords)
Saussurea lappa
dehydrocostus lactone
soft tissue sarcoma
cell cycle analysis
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