Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/16172
Title: A recombinant fragment of Human Surfactant Protein D induces apoptosis in pancreatic cancer cell lines via Fas-mediated pathway
Authors: Kaur, A
Riaz, MS
Murugaiah, V
Varghese, PM
Singh, SK
Kishore, U
Keywords: Pancreatic cancer;Innate immunity;Surfactant protein;SP-D;Apoptosis;Immune surveillance
Issue Date: 2018
Citation: Frontiers in Immunology
Abstract: Human Surfactant Protein (SP-D) is a potent innate immune molecule, which is emerging as a key molecule in the recognition and clearance of altered and non-self targets. Previous studies have shown that a recombinant fragment of human SP-D (rfhSP-D) induced apoptosis via p53 mediated apoptosis pathway in an eosinophilic leukemic cell line, AML14.3D10. Here, we report the ability of rfhSP-D to induce apoptosis via TNF-α/Fas-mediated apoptosis pathway regardless of the p53 status in human pancreatic adenocarcinoma using Panc-1 (p53mt), MiaPaCa-2 (p53mt), and Capan-2 (p53wt) cell lines. Treatment of these cell lines with rfhSP-D for 24 h caused growth arrest in G1 cell cycle phase and triggered transcriptional upregulation of proapoptotic factors such as TNF-α and NF-κB. Translocation of NF-κB from the cytoplasm into the nucleus of pancreatic cancer cell lines was observed via immunofluorescence microscopy following treatment with rfhSP-D as compared to the untreated cells. The rfhSP-D treatment caused upregulation of pro-apoptotic marker Fas, as analyzed via qPCR and western blot, which then triggered caspase cascade, as evident from cleavage of caspase 8 and 3 analyzed via western blot at 48 h, and subsequent, apoptosis of the cells. The cell number following the rfhSP-D treatment was reduced in the order of Panc-1 (~67%) > MiaPaCa-2 (~60%) > Capan2 (~35%). Our studies appear to suggest that rfhSP-D can be used to therapeutically target pancreatic cancer cells irrespective of their p53 phenotype.
URI: https://www.frontiersin.org/articles/10.3389/fimmu.2018.01126/abstract
http://bura.brunel.ac.uk/handle/2438/16172
DOI: http://dx.doi.org/10.3389/fimmu.2018.01126
ISSN: 1664-3224
Appears in Collections:Dept of Life Sciences Research Papers

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