Phytotherapeutics oridonin and ponicidin show additive effects combined with irradiation in pancreatic cancer in vitro

• Verfasst von: Liermann, Jakob [VerfasserIn]
• Verfasst von: Naumann, Patrick [VerfasserIn]
• Verfasst von: Fortunato, Franco [VerfasserIn]
• Verfasst von: Weber, Klaus-Josef [VerfasserIn]
• Verfasst von: Debus, Jürgen [VerfasserIn]
• Titel: Phytotherapeutics oridonin and ponicidin show additive effects combined with irradiation in pancreatic cancer in vitro
• Verf.angabe: Jakob Liermann, Patrick Naumann, Franco Fortunato, Thomas E. Schmid, Klaus-Josef Weber, Jürgen Debus, Stephanie E. Combs
• Umfang: 8 S.
• Fussnoten: Gesehen am 07.03.2018
• Titel Quelle: Enthalten in: Radiology and oncology
• Jahr Quelle: 2017
• Band/Heft Quelle: 51(2017), 4, S. 407-414
• ISSN Quelle: 1581-3207
• DOI: doi:10.1515/raon-2017-0048
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1570616973
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

Background: Chemoradiation of locally advanced non-metastatic pancreatic cancer can lead to secondary operability by tumor mass reduction. Here, we analyzed radiomodulating effects of oridonin and ponicidin in pancreatic cancer in vitro. Both agents are ent-kaurane diterpenoids, extracted from Isodon rubescens, a plant that is well known in Traditional Chinese Medicine. Cytotoxic effects have recently been shown in different tumor entities for both agents. Materials and methods: Pancreatic cancer cell lines AsPC-1, BxPC-3, Panc-1 and MIA PaCa-2 were pretreated with oridonin or ponicidin and irradiated with 2 Gy to 6 Gy. Long-term survival was determined by clonogenic assay. Cell cycle effects and intensity of γH2AX as indicator for DNA double-strand breaks were investigated by flow cytometry. Western blotting was used to study the DNA double-strand break repair proteins Ku70, Ku80 and XRCC4. Results: Oridonin and ponicidin lead to a dose-dependent reduction of clonogenic survival and an increase in γH2AX. Combined with irradiation we observed additive effects and a prolonged G2/M-arrest. No relevant changes in the levels of the DNA double-strand break repair proteins were detected. Conclusions: Pretreatment with oridonin or ponicidin followed by irradiation lead to an additional reduction in survival of pancreatic cancer cells in vitro, presumably explained by an induced prolonged G2/M-arrest. Both agents seem to induce DNA double-strand breaks but do not interact with the non-homologous end joining (NHEJ) pathway.