ArticleStem cell research & therapy2015
Polyphenols from marine brown algae target radiotherapy-coordinated EMT and stemness-maintenance in residual pancreatic cancer.
Article in Stem cell research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 33 citations in OpenAlex.
- Network pharmacology and experimental study on the inhibition of glycolysis by amentoflavone in pancreatic cancer.Discover oncology · 2025Article
- The ufmylation modification of ribosomal protein L10 in the development of pancreatic adenocarcinoma.Cell death & disease · 2023Article
- Marine-Inspired Drugs and Biomaterials in the Perspective of Pancreatic Cancer Therapies.Marine drugs · 2022Review
- HuR Affects the Radiosensitivity of Esophageal Cancer by Regulating the EMT-Related Protein Snail.Frontiers in oncology · 2022Article
- The plasticity of pancreatic cancer stem cells: implications in therapeutic resistance.Cancer metastasis reviews · 2021Review
- Squalene deters drivers of RCC disease progression beyond VHL status.Cell biology and toxicology · 2021Article
- Polyphenols as Possible Agents for Pancreatic Diseases.Antioxidants (Basel, Switzerland) · 2020Review
- The Protective Effect of Polyphenols for Colorectal Cancer.Frontiers in immunology · 2020Review
- Targeting acquired oncogenic burden in resilient pancreatic cancer: a novel benefit from marine polyphenols.Molecular and cellular biochemistry · 2019Article
- Dietary Phytochemicals Targeting Cancer Stem Cells.Molecules (Basel, Switzerland) · 2019Review
- Interleukin-23 receptor signaling mediates cancer dormancy and radioresistance in human esophageal squamous carcinoma cells via the Wnt/Notch pathway.Journal of molecular medicine (Berlin, Germany) · 2019Article
- Ruanjian Sanjie decoction exhibits antitumor activity by inducing cell apoptosis in breast cancer.Oncology letters · 2017Article
- Hormophysa triquerta polyphenol, an elixir that deters CXCR4- and COX2-dependent dissemination destiny of treatment-resistant pancreatic cancer cells.Oncotarget · 2017Article
- High Energy Particle Radiation-associated Oncogenic Transformation in Normal Mice: Insight into the Connection between Activation of Oncotargets and Oncogene Addiction.Scientific reports · 2016Article
- Radiation induces the generation of cancer stem cells: A novel mechanism for cancer radioresistance.Oncology letters · 2016Article
- Exploiting Gene Expression Kinetics in Conventional Radiotherapy, Hyperfractionation, and Hypofractionation for Targeted Therapy.Seminars in radiation oncology · 2016Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionTherapy-associated onset of stemness-maintenance in surviving tumor-cells dictates tumor relapse/recurrence. Recently, we recognized the anti-pancreatic cancer (PC) potential of seaweed polyphenol manifolds and narrowed down three superior drug-deliverables that could serve as adjuvants and benefit PC cure. Utilizing the PC- cancer stem cells (PC-CSCs) grown ex vivo and mouse model of residual-PC, we investigated the benefits of seaweed polyphenols in regulating stemness-maintenance.
methodsALDH(+)CD44(+)CD24(+) PC-CSCs from Panc-1, Panc-3.27, MiaPaCa-2, or BxPC-3 cells-derived xenografts grown ex vivo were either mock-irradiated, exposed to fractionated irradiation (FIR, 2Gy/D for 5 days), treated with polyphenols (100 μg/ml) of Hormophysa triquerta (HT-EA), Spatoglossum asperum (SA-EA) or Padina tetrastromatica (PT-EA) with/without FIR were examined for cell viability, transcription of 93 stem-cell-related molecules (QPCR profiling). Polyphenol-dependent regulation of FIR-transactivated Oct4, Zic3, EIF4C, Nanog, and LIF (QPCR) and functional translation of Nanog, SOX2, and OCT3/4 (immunoblotting) were examined in Panc-1/Panc-3.27/MiaPaCa-2/BxPC-3-xenografts derived PC-CSCs. Effect of seaweed-polyphenols in the regulation of EMT (N-Cadherin), pluripotency- (SOX2, OCT3/4, Nanog) and stemness-maintenance (PI3KR1, LIF, CD44) in therapy (FIR, 2Gy/D for 5D/wk for 3-weeks) resistant residual tumors were examined by tissue microarray construction and automated immunohistochemistry.
resultsEx vivo exposure of PC-CSCs to SA-EA, PT-EA and HT-EA exhibit dose-dependent inhibition of cell viability. FIR amplified the transcription of 69, 80, 74 and 77 stem-cell related genes in MiaPaCa-2-, Panc-1-, Panc-3.27- and BXPC3-established xenograft-derived ALDH(+)CD44(+)CD24(+)PC-CSCs. Treatment with SA-EA, PT-EA, or HT-EA completely suppressed FIR-activated stem-cell transcriptional machinery in ALDH(+)CD44(+)CD24(+)PC-CSCs established from MiaPaCa-2, Panc-1, Panc-3.27 and BXPC3 xenografts. QPCR validated EIF4C, OCT3/4, Nanog, LIF, and ZIC3 transcriptional profile outcomes. Nanog, Sox2, and OCT3/4 immunoblotting affirmed the PC-CSC radiosensitizing benefit of seaweed polyphenols. Residual-PC tissues microarrayed and immunostained after in vivo treatments recognized complete regulation of FIR-induced SOX2, OCT3/4, Nanog, LIF, CD44, PIK3R1, N-Cadherin, and E-Cadherin with SA-EA, PT-EA, and HT-EA.
conclusionsThese data, for the first time, documented the EMT/stemness-maintenance in therapy-resistant PC-CSCs. Further, the data suggest that seaweed polyphenols may inhibit PC relapse/recurrence by targeting therapy-orchestrated stem-cell signaling in residual cells.
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