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Effect of 5-aminolevulinic acid on the haem biosynthesis pathway in pancreatic cancer and pancreatic ductal epithelial cell lines

Labib, PL; Al-Akkad, W; Davidson, BR; MacRobert, AJ; Pereira, SP; (2019) Effect of 5-aminolevulinic acid on the haem biosynthesis pathway in pancreatic cancer and pancreatic ductal epithelial cell lines. In: 17th International Photodynamic Association World Congress. (pp. 110706K). SPIE: Cambridge, Massachusetts, United States. Green open access

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Abstract

Introduction: 5-aminolevulinic acid (ALA) generates protoporphyrin IX (PpIX)-induced fluorescence by acting as a substrate for the haem biosynthesis pathway. Despite suggestions that ALA could be used for pancreatic cancer photodiagnostics, the pancreatic cancer cell line PANC-1 only shows weak fluorescence following ALA administration. A possible explanation was that the haem biosynthesis pathway varies between cancers. Methods: We compared the mRNA expression of the haem biosynthesis pathway of PANC-1 (weak fluorescence) with the pancreatic cancer cell line CFPAC-1 (strong fluorescence) and the pancreatic ductal cell line H6c7 (control) with or without 24 hours ALA incubation. Cells were seeded on day one, fresh media with or without ALA (0.5mM) added on day two, and RNA extracted on day three. Quantitative real-time polymerase chain reaction was performed to assess the relative mRNA expression of four membrane transporters and eight enzymes responsible for haem biosynthesis. Results: Post-ALA incubation, CFPAC-1 demonstrated significant downregulation of cell membrane ALA influx transporter PEPT1, downregulation of ALA synthase and upregulation of the mitochondrial membrane transporter ABCB6. PANC-1, whilst showing similar changes to ALA synthase and ABCB6, showed significant upregulation of the PpIX efflux transporter ABCG2. PANC-1 also had minimal PEPT1 expression pre- and post-ALA. H6c7 demonstrated significant up- or downregulation of three transporters and five enzymes. Conclusion: Poor PpIX-induced fluorescence in PANC-1 is likely to be secondary to decreased ALA influx from low PEPT1 expression and increased ABCG2 expression. The use of nanocarriers to deliver ALA and/or ABCG2 inhibitors may improve ALA-induced fluorescence in PANC-1 and other ALA-resistant cancers.

Type: Proceedings paper
Title: Effect of 5-aminolevulinic acid on the haem biosynthesis pathway in pancreatic cancer and pancreatic ductal epithelial cell lines
Event: 17th International Photodynamic Association World Congress
Location: Cambridge, Massachusetts, United States
Dates: 28 June 2019 - 04 July 2019
ISBN-13: 9781510628335
Open access status: An open access version is available from UCL Discovery
DOI: 10.1117/12.2525085
Publisher version: https://doi.org/10.1117/12.2525085
Language: English
Additional information: This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: 5-aminolevulinic acid, ALA, haem biosynthesis pathway, pancreatic cancer, photodiagnostics, PEPT1, ABCG2
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
URI: https://discovery.ucl.ac.uk/id/eprint/10079657
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