A eudesmane-type sesquiterpene isolated from <i>Pluchea odorata</i> (L.) Cass. combats three hallmarks of cancer cells
- Author(s)
- Michael Blaschke, Ruxandra McKinnon, Chi Huu Nguyen, Silvio Holzner, Martin Zehl, Atanas Georgiev Atanasov, Karin Schelch, Sigurd Krieger, Rene Diaz, Richard Frisch, Bjoern Feistel, Walter Jäger, Gerhard F. Ecker, Verena M. Dirsch, Michael Grusch, Istvan Zupko, Ernst Urban, Brigitte Kopp, Georg Krupitza
- Abstract
Pluchea odorata is ethno pharmaceutically used to treat inflammation-associated disorders. The dichloromethane extract (DME) was tested in the carrageenan-induced rat paw oedema assay investigating its effect on inflammation that was inhibited by 37%. Also an in vitro anti-neoplastic potential was reported. However, rather limited information about the bio-activity of purified compounds and their cellular mechanisms are available. Therefore, two of the most abundant eudesmanes in P. odorata were isolated and their anti-neoplastic and anti-intravasative activities were studied. HL-60 cells were treated with P. odorata compounds and metabolic activity, cell number reduction, cell cycle progression and apoptosis induction were correlated with relevant protein expression. Tumour cell intravasation through lymph endothelial monolayers was measured and potential causal mechanisms were analyzed by Western blotting. Compound PO-1 decreased the metabolic activity of HL-60 cells (IC50=8.9μM after 72h) and 10μM PO-1 induced apoptosis, while PO-2 showed just weak anti-neoplastic activities at concentrations beyond 100μM. PO-1 arrested the cell cycle in G1 and this correlated with induction of JunB expression. Independent of this mechanism 25μM PO-1 decreased MCF-7 spheroid intravasation through the lymph endothelial barrier. Hence, PO-1 inhibits an early step of metastasis, impairs unrestricted proliferation and induces apoptosis at low micromolar concentrations. These results warrant further testing in vivo to challenge the potential of PO-1 as novel lead compound.
- Organisation(s)
- External organisation(s)
- Medizinische Universität Wien, Finzelberg GmbH & Co KG, University of Szeged, Institute for Ethnobiology, Playa Diana, San José, Petén, Guatemala.
- Journal
- Mutation Research: fundamental and molecular mechanisms of mutagenesis
- Volume
- 777
- Pages
- 79-90
- No. of pages
- 12
- ISSN
- 1386-1964
- DOI
- https://doi.org/10.1016/j.mrfmmm.2015.04.011
- Publication date
- 05-2015
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 301904 Cancer research, 301207 Pharmaceutical chemistry, 301204 Pharmacognosy
- Keywords
- ASJC Scopus subject areas
- Genetics, Molecular Biology, Health, Toxicology and Mutagenesis
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/4d323de3-d2ac-427a-908b-6134244d2e02