ArticleJournal of biomedical science2015
Novel adjuvants from seaweed impede autophagy signaling in therapy-resistant residual pancreatic cancer.
Article in Journal of biomedical science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 21 citations in OpenAlex.
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- Marine-Inspired Drugs and Biomaterials in the Perspective of Pancreatic Cancer Therapies.Marine drugs · 2022Review
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- Regulation and function of autophagy in pancreatic cancer.Autophagy · 2021Review
- Targeting acquired oncogenic burden in resilient pancreatic cancer: a novel benefit from marine polyphenols.Molecular and cellular biochemistry · 2019Article
- Droplet digital PCR as an alternative to FISH for MYCN amplification detection in human neuroblastoma FFPE samples.BMC cancer · 2019Article
- Retinal Degeneration Protein 3 (RD3) in normal human tissues: Novel insights.Scientific reports · 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
- Exploiting Gene Expression Kinetics in Conventional Radiotherapy, Hyperfractionation, and Hypofractionation for Targeted Therapy.Seminars in radiation oncology · 2016Review
- Blue-Print Autophagy: Potential for Cancer Treatment.Marine drugs · 2016Review
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIdentifying the drug-deliverables that target autophagy is crucial to finding a cure for pancreatic cancer (PC), as activated autophagy is associated with poor patient outcomes. Our recent studies recognized the anti-PC potential of an antioxidant-rich collection of seaweed polyphenols and identified potential compounds for the treatment of PC. Accordingly, we investigated whether such compounds could regulate autophagy in therapy-resistant PC cells in vitro and in residual PC in vivo.
resultsHuman Panc-3.27 and MiaPaCa-2 cells were exposed to fractionated irradiation (FIR) with/without ethyl acetate (EA) polyphenol from Spatoglossum asperum (SA-EA), Padina tetrastromatica (PT-EA), or Hormophysa triquerta (HT-EA). The cells were subjected to QPCR to examine transcriptional alterations in the following autophagy functional regulators: ATG3, ATG5, ATG7, ATG12, LC3A, LC3B, Beclin, Myd88, HMGB1, Rage, and TLRs 1-9. Using a clinically relevant mouse model of residual PC, we use tissue microarray (TMA) and immunohistochemistry (IHC) procedures to investigate the potential of polyphenol(s) to target ATG3, ATG5, ATG12, LC3A, LC3B, BECN1, and SURIVIN after clinical radiotherapy. Radiation significantly increased the transcription of autophagy functional regulators in both cell lines. Seaweed polyphenols completely suppressed the transcription of all investigated autophagy regulators in both cell-lines. Gene silencing approach defined the role of LC3B in radiation-induced cell survival in this setting. TMA-IHC analysis revealed the complete regulation of ATG3, ATG5, ATG12, LC3A, LC3B, BECN1, and SURVIVIN in residual PC following SA-EA, PT-EA, and HT-EA treatment.
conclusionsThese data demonstrate the autophagy blue print in therapy-resistant PC cells for the first time. Moreover, the data strongly suggest that the selected polyphenols could serve as effective adjuvants for current PC treatment modalities and may inhibit tumor relapse by comprehensively targeting therapy-orchestrated autophagy in residual cells.
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