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

Sulforaphane enhances irradiation effects in terms of perturbed cell cycle progression and increased DNA damage in pancreatic cancer cells.

PLoS ONE 12:e0180940 (2017)

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Background Sulforaphane (SFN), an herbal isothiocyanate enriched in cruciferous vegetables like broccoli and cauliflower, has gained popularity for its antitumor effects in cell lines such as pancreatic cancer. Antiproliferative as well as radiosensitizing properties were reported for head and neck cancer but little is known about its effects in pancreatic cancer cells in combination with irradiation (RT). Methods In four established pancreatic cancer cell lines we investigated clonogenic survival, analyzed cell cycle distribution and compared DNA damage via flow cytometry and western blot after treatment with SFN and RT. Results Both SFN and RT show a strong and dose dependent survival reduction in clonogenic assays, an induction of a G2/M cell cycle arrest and an increase in ?H2AX protein level indicating DNA damage. Effects were more pronounced in combined treatment and both cell cycle perturbation and DNA damage persisted for a longer period than after SFN or RT alone. Moreover, SFN induced a loss of DNA repair proteins Ku 70, Ku 80 and XRCC4. Conclusion Our results suggest that combination of SFN and RT exerts a more distinct DNA damage and growth inhibition than each treatment alone. SFN seems to be a viable option to improve treatment efficacy of chemoradiation with hopefully higher rates of secondary resectability after neoadjuvant treatment for pancreatic cancer.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Strand Break Repair; Oxidative Stress; Neoadjuvant Chemoradiation; Gamma-h2ax; Radiation; Arrest; Chemotherapy; Apoptosis; Pathways; Biology

ISSN (print) / ISBN 1932-6203

Journal PLoS ONE

Quellenangaben Volume: 12, Issue: 7, Article Number: e0180940

Publisher Public Library of Science (PLoS)

Publishing Place Lawrence, Kan.

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Radiation Medicine (IRM)