Funded in part by Bayer Corporation
Synergistic activity of sorafenib and sulforaphane abolishes pancreatic cancer stem cell characteristics
Rausch V, Liu L, Kallifatidis G, Baumann B, Mattern J, Gladkich J, Wirth T, Schemmer P, Büchler MW, Zöller M, Salnikov AV, Herr I
Cancer research · 147 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Industry funded
- Company
- Bayer Corporation
- Government
- China Scholarship Council
Based on 2 listed funder(s).
Publication
- Published
- 2010-06-08 · Cancer Res · vol. 70 · issue 12 · pp. 5004–5013
- Publisher
- American Association for Cancer Research
- Cited
- 210 citations · more than 99% of similar papers · 9.2× the field average
- Impact
- Top 10% most cited in its field
- References
- 38 works
- Access
- Paywalled
- Research areas
- Genomics, phytochemicals, and oxidative stress · PI3K/AKT/mTOR signaling in cancer · Quinazolinone synthesis and applications
- Keywords
- Sulforaphane, Pancreatic cancer, Downregulation and upregulation, Cancer research, Sorafenib, Angiogenesis, Apoptosis, Cancer stem cell, Epithelial–mesenchymal transition, Cell growth, Cancer, Metastasis, Cancer cell, Stem cell, Chemistry, Biology, Medicine, Cell biology, Internal medicine, Biochemistry, Hepatocellular carcinoma
- MeSH
- cells, cultured, spheroids, cellular, fibroblasts, skin, animals, humans, mice, mice, nude, pancreatic neoplasms, neovascularization, pathologic, thiocyanates, benzenesulfonates, isothiocyanates, sulfoxides, phenylurea compounds, niacinamide, pyridines, isoenzymes, aldehyde dehydrogenase, luciferases, nf-kappa b, rna, messenger, antineoplastic combined chemotherapy protocols, immunoblotting, blotting, western, immunoenzyme techniques, electrophoretic mobility shift assay, colony-forming units assay, xenograft model antitumor assays, reverse transcriptase polymerase chain reaction, apoptosis, cell proliferation, drug synergism, female, retinal dehydrogenase, neoplastic stem cells, sorafenib, aldehyde dehydrogenase 1 family
12 authors
From DE
- Vanessa RauschGerman Cancer Research Center; Universität Ulm; Heidelberg University
- Li LiuGerman Cancer Research Center; Universität Ulm; Heidelberg University
- Georgios KallifatidisGerman Cancer Research Center; Universität Ulm; Heidelberg University
- Bernd BaumannGerman Cancer Research Center; Universität Ulm; Heidelberg University
- Jürgen MatternGerman Cancer Research Center; Universität Ulm; Heidelberg University
- Jury GladkichGerman Cancer Research Center; Universität Ulm; Heidelberg University
Abstract
Recent evidence suggests that pancreatic cancer and other solid tumors contain a subset of tumorigenic cells capable of extensive self-renewal that contribute to metastasis and treatment resistance. Sorafenib (SO) is a promising new multikinase inhibitor for treatment of advanced kidney and liver cancers. We report here targeting of pancreatic cancer stem cells (CSC) by SO and the development of a strategy to enhance this effect. Although SO administration diminished clonogenicity, spheroid formation, aldehyde dehydrogenase 1 (ALDH1) activity, growth on immunodeficient mice, proliferation, and angiogenesis and induced apoptosis, we observed SO-induced activation of NF-kappaB associated with survival and regrowth of spheroids. For enhanced elimination of CSC characteristics by SO, we cotreated cells with sulforaphane (SF). This broccoli isothiocyanate was recently described to eliminate pancreatic CSCs by downregulation of NF-kappaB activity without inducing toxic side effects. On combination treatment, SF completely eradicated SO-induced NF-kappaB binding, which was associated with abrogated clonogenicity, spheroid formation, ALDH1 activity, migratory capacity, and induction of apoptosis. In vivo, combination therapy reduced the tumor size in a synergistic manner. This was due to induction of apoptosis, inhibition of proliferation and angiogenesis, and downregulation of SO-induced expression of proteins involved in epithelial-mesenchymal transition. Our data suggest that SF may be suited to increase targeting of CSCs by SO.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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