Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Naumann P

PROVIDER: S-EPMC5507286 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

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

Naumann Patrick P Liermann Jakob J Fortunato Franco F Schmid Thomas E TE Weber Klaus-Josef KJ Debus Jürgen J Combs Stephanie E SE

PloS one 20170710 7

<h4>Background</h4>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).<h4>Methods</h4>In four established pancreatic cancer cell lines we investigated cl ...[more]

PMID: 28700650

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Project description:Increased cell senescence contributes to the pathogenesis of aging and aging-related disease. Senescence of human fibroblasts in vitro may be delayed by culture in low glucose concentration. There is also accumulating evidence of senescence delay by exposure to dietary bioactive compounds that activate transcription factor Nrf2. The mechanism of cell senescence delay and connection between these responses is unknown. We describe herein that the cruciferous vegetable-derived metabolite, sulforaphane (SFN), activates Nrf2 and delays senescence of human MRC-5 and BJ fibroblasts in vitro. Cell senescence is associated with a progressive and marked increased rate of glucose metabolism through glycolysis. This increases mitochondrial dysfunction and overwhelms defences against reactive metabolites, leading to increasing proteomic and genomic oxidative damage. Increased glucose entry into glycolysis in fibroblast senescence is mainly mediated by increased hexokinase-2. SFN delayed senescence by decreasing glucose metabolism on the approach to senescence, exhibiting a caloric restriction mimetic-like activity and thereby decreased oxidative damage to cell protein and DNA. This was associated with increased expression of thioredoxin-interacting protein, curbing entry of glucose into cells; decreased hexokinase-2, curbing entry of glucose into cellular metabolism; decreased 6-phosphofructo-2-kinase, downregulating formation of allosteric enhancer of glycolysis fructose-2,6-bisphosphate; and increased glucose-6-phosphate dehydrogenase, downregulating carbohydrate response element- (ChRE-) mediated transcriptional enhancement of glycolysis by Mondo/Mlx. SFN also enhanced clearance of proteins cross-linked by transglutaminase which otherwise increased in senescence. This suggests that screening of compounds to counter senescence-associated glycolytic overload may be an effective strategy to identify compounds with antisenescence activity and health beneficial effects of SFN in longevity may involve delay of senescence through glucose and glycolytic restriction response.

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

Similar Datasets

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