<abstract xmlns="http://www.w3.org/1999/xhtml"><sec id="j_raon-2017-0048_s_006_w2aab3b7c10b1b6b1aab1c19b1Aa"><h3>Background</h3><p>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 <italic>in vitro</italic>. Both agents are ent-kaurane diterpenoids, extracted from <italic>Isodon rubescens</italic>, a plant that is well known in Traditional Chinese Medicine. Cytotoxic effects have recently been shown in different tumor entities for both agents.</p></sec><sec id="j_raon-2017-0048_s_007_w2aab3b7c10b1b6b1aab1c19b2Aa"><h3>Materials and methods</h3><p>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.</p></sec><sec id="j_raon-2017-0048_s_008_w2aab3b7c10b1b6b1aab1c19b3Aa"><h3>Results</h3><p>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.</p></sec><sec id="j_raon-2017-0048_s_009_w2aab3b7c10b1b6b1aab1c19b4Aa"><h3>Conclusions</h3><p>Pretreatment with oridonin or ponicidin followed by irradiation lead to an additional reduction in survival of pancreatic cancer cells <italic>in vitro</italic>, 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.</p></sec></abstract>

BackgroundChemoradiation 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 methodsPancreatic 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.ResultsOridonin 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.ConclusionsPretreatment 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.

Phytotherapeutics oridonin and ponicidin show additive effects combined with irradiation in pancreatic cancer <italic>in vitro</italic>

Department of Radiation Oncology, Klinikum rechts der Isar

Radiology and Oncology

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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

BackgroundChemoradiation of locally advanced non-metastatic pancreatic cancer can lead to secondary operability by tumor mass reduction. Here, we analyzed...

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

Article Category: Research Article

Published Online: Nov 29, 2017

Page range: 407 - 414

Received: Jun 28, 2017

Accepted: Oct 13, 2017

DOI: https://doi.org/10.1515/raon-2017-0048

© 2017 Jakob Liermann, Patrick Naumann, Franco Fortunato, Thomas E. Schmid, Klaus-Josef Weber, Jürgen Debus, Stephanie E. Combs

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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