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

  • Jakob Liermann Department of Radiation Oncology, Heidelberg University Hospital, INF 400, 69120 Heidelberg, Germany
  • Patrick Naumann Department of Radiation Oncology, Heidelberg University Hospital, INF 400, 69120 Heidelberg, Germany
  • Franco Fortunato Heidelberg University Hospital, Section Surgical Research, INF 365, 69120 Heidelberg, Germany
  • Thomas E Schmid Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675 Munich, Germany
  • Klaus-Josef Weber Department of Radiation Oncology, Heidelberg University Hospital, INF 400, 69120 Heidelberg, Germany
  • Jürgen Debus Department of Radiation Oncology, Heidelberg University Hospital, INF 400, 69120 Heidelberg, Germany
  • Stephanie E Combs Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, D 81675 Munich, Germany. Institute of Innovative Radiotherapy (iRT), Department of Radiation Sciences (DRS), Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany

Abstract

Introduction

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.

 

Material 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 NHEJ pathway.

Published
2017-11-27
How to Cite
Liermann, J., Naumann, P., Fortunato, F., Schmid, T. E., Weber, K.-J., Debus, J., & Combs, S. E. (2017). Phytotherapeutics oridonin and ponicidin show additive effects combined with irradiation in pancreatic cancer in vitro. Radiology and Oncology, 51(4). Retrieved from https://www.radioloncol.com/index.php/ro/article/view/2931
Section
Experimental oncology