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Phytotherapeutics Oridonin and Ponicidin show Additive Effects Combined with Irradiation in Pancreatic Cancer in Vitro .
- Source :
-
Radiology and oncology [Radiol Oncol] 2017 Nov 29; Vol. 51 (4), pp. 407-414. Date of Electronic Publication: 2017 Nov 29 (Print Publication: 2017). - Publication Year :
- 2017
-
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.<br />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.<br />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.<br />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.<br />Competing Interests: Disclosure: No potential conflicts of interest were disclosed.
Details
- Language :
- English
- ISSN :
- 1318-2099
- Volume :
- 51
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Radiology and oncology
- Publication Type :
- Academic Journal
- Accession number :
- 29333119
- Full Text :
- https://doi.org/10.1515/raon-2017-0048