Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Lohberger, B; Rinner, B; Stuendl, N; Kaltenegger, H; Steinecker-Frohnwieser, B; Bernhart, E; Bonyadi Rad, E; Weinberg, AM; Leithner, A; Bauer, R; Kretschmer, N.
Sesquiterpene lactones downregulate G2/M cell cycle regulator proteins and affect the invasive potential of human soft tissue sarcoma cells.
PLoS One. 2013; 8(6):e66300-e66300
Doi: 10.1371/journal.pone.0066300
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- Leading authors Med Uni Graz
- Lohberger Birgit
- Co-authors Med Uni Graz
- Bernhart Eva Maria
- Bonyadirad Ehsan
- Eck Nicole
- Kaltenegger Heike
- Kretschmer Nadine
- Leithner Andreas
- Rinner Beate
- Steinecker-Frohnwieser Bibiane
- Weinberg Annelie-Martina
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- Abstract:
- Soft tissue sarcomas (STS) represent a rare group of malignant tumors that frequently exhibit chemotherapeutic resistance and increased metastatic potential. Many studies have demonstrated the great potential of plant-derived agents in the treatment of various malignant entities. The present study investigates the effects of the sesquiterpene lactones costunolide and dehydrocostus lactone on cell cycle, MMP expression, and invasive potential of three human STS cell lines of various origins. Both compounds reduced cell proliferation in a time- and dose-dependent manner. Dehydrocostus lactone significantly inhibited cell proliferation, arrested the cells at the G2/M interface and caused a decrease in the expression of the cyclin-dependent kinase CDK2 and the cyclin-dependent kinase inhibitor p27(Kip1). In addition, accumulation of cells at the G2/M phase transition interface resulted in a significant decrease in cdc2 (CDK1) together with cyclin B1. Costunolide had no effect on the cell cycle. Based on the fact that STS tend to form daughter cell nests and metastasize, the expression levels of matrix metalloproteinases (MMPs), which play a crucial role in extracellular matrix degradation and metastasis, were investigated by Luminex® technology and real-time RT-PCR. In the presence of costunolide, MMP-2 and -9 levels were significantly increased in SW-982 and TE-671 cells. Dehydrocostus lactone treatment significantly reduced MMP-2 and -9 expression in TE-671 cells, but increased MMP-9 level in SW-982 cells. In addition, the invasion potential was significantly reduced after treatment with both sesquiterpene lactones as investigated by the HTS FluoroBlock™ insert system.
- Find related publications in this database (using NLM MeSH Indexing)
- Antineoplastic Agents - pharmacology
- Cell Line, Tumor -
- Cell Proliferation - drug effects
- Cell Survival - drug effects
- Collagenases - genetics
- Collagenases - metabolism
- Cyclin-Dependent Kinase 2 - genetics
- Cyclin-Dependent Kinase 2 - metabolism
- Cyclin-Dependent Kinase Inhibitor p27 - genetics
- Cyclin-Dependent Kinase Inhibitor p27 - metabolism
- Down-Regulation -
- Drug Screening Assays, Antitumor -
- G2 Phase Cell Cycle Checkpoints - drug effects
- Gene Expression - drug effects
- High-Throughput Screening Assays -
- Humans -
- Lactones - pharmacology
- Neoplasm Invasiveness -
- Sarcoma - pathology
- Sesquiterpenes - pharmacology
- Tumor Suppressor Protein p53 - genetics
- Tumor Suppressor Protein p53 - metabolism