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Liermann, J.* ; Naumann, P.S.* ; Fortunato, F.* ; Schmid, T.E.* ; Weber, K.* ; Debus, J.* ; Combs, S.E.

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

Radiol. Oncol. 51, 407-414 (2017)
Verlagsversion DOI
Open Access Gold
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 gamma H2AX 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 gamma H2AX. 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Oridonin ; Ponicidin ; Irradiation ; Pancreatic Cancer;.h2ax ; Radiosensitivity; Nf-kappa-b; Rabdosia-rubescens; Cell-growth; Antitumor-activity; Apoptosis; Induction; Pathways; Diterpenoids; Mechanisms; Expression
ISSN (print) / ISBN 1318-2099
e-ISSN 1581-3207
Quellenangaben Band: 51, Heft: 4, Seiten: 407-414 Artikelnummer: , Supplement: ,
Verlag Inst. of Oncology
Verlagsort Ljubljana
Begutachtungsstatus Peer reviewed