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Updated: Apr 3, 2026
Isolation of Stem Cells from Human Pancreatic Cancer Xenografts
Published on: September 26, 2010
Polyphenols from marine brown algae target radiotherapy-coordinated EMT and stemness-maintenance in residual
Sheeja Aravindan1,2, Satish Kumar Ramraj3, Somasundaram T Somasundaram4
1Department of Marine Sciences, Center of Advance Study in Marine Biology, Annamalai University, Parangipettai, TN, 608 502, India. saravind@ouhsc.edu.
Introduction:
Therapy-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.
Methods:
ALDH(+)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.
Results:
Ex 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.
Conclusions:
These 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.
Insights
Seaweed polyphenols inhibit pancreatic cancer stem cell recurrence by targeting therapy-induced stemness. These compounds suppress key genes involved in cancer stem cell survival and recurrence, offering a novel therapeutic strategy.
Area of Science:
- Marine natural products chemistry
- Cancer stem cell biology
- Pancreatic cancer therapeutics
Background:
- Therapy resistance in pancreatic cancer (PC) is often driven by stemness maintenance in surviving tumor cells, leading to relapse.
- Seaweed polyphenols show potential as anti-PC agents and adjuvants.
- Investigating seaweed polyphenols' effect on PC stemness is crucial for improving treatment outcomes.
Purpose of the Study:
- To investigate the efficacy of specific seaweed polyphenols (Hormophysa triquerta, Spatoglossum asperum, Padina tetrastromatica) in regulating stemness maintenance in pancreatic cancer stem cells (PC-CSCs).
- To evaluate the potential of these polyphenols as adjuvants to fractionated irradiation (FIR) in overcoming therapy resistance.
Main Methods:
- PC-CSCs (ALDH(+)CD44(+)CD24(+)) from various pancreatic cancer cell lines were treated with seaweed polyphenol extracts (HT-EA, SA-EA, PT-EA) with or without FIR.
- Cell viability, stem-cell-related gene transcription (QPCR), protein expression (immunoblotting), and markers of epithelial-mesenchymal transition (EMT) and pluripotency were analyzed.
- In vivo studies utilized tissue microarrays of residual tumor tissues from treated mice.
Main Results:
- Seaweed polyphenols inhibited PC-CSC viability in a dose-dependent manner.
- Polyphenol treatment completely suppressed FIR-activated stemness-related gene transcription and key protein expression (Oct4, Nanog, SOX2).
- In vivo analysis showed regulation of EMT, pluripotency, and stemness markers in residual tumors treated with seaweed polyphenols.
Conclusions:
- This study provides the first evidence of EMT and stemness maintenance in therapy-resistant PC-CSCs.
- Seaweed polyphenols demonstrate potential in inhibiting pancreatic cancer relapse by targeting therapy-induced stem cell signaling in residual cells.
