Analysis of cell line variation in biochemical production of protoporphyrin IX

Summer L. Gibbs, Bin Chen, Julia A. Ohara, P. Jack Hoopes, Tayyaba Hasan, Brian W. Pogue

Research output: Chapter in Book/Report/Conference proceedingConference contribution

2 Scopus citations

Abstract

Protoporphyrin IX (PpIX) is produced via the heme synthesis pathway by the cell following administration of aminolevulinic acid (ALA). ALA synthase, the enzyme that produces ALA in the cell from glycine and succinylcoenzyme A, is inhibited in a feedback mechanism by heme and thus is the rate limiting enzyme in the heme synthesis pathway. Since ALA is administered systemically, the rate limiting step that naturally exists in the cells is bypassed, however it is currently unclear why cells have different rate limiting steps in the ALA-PpIX synthesis pathway, and more specifically which types of cancer cells are most productive. It has been determined that when the same amount of ALA is administered to a wide panel of cancer cells in vitro that vastly differing amounts of PpIX are produced. The steps for the ALA-PpIX pathway occur in and around the mitochondria of the cell, but interestingly no correlation is seen between PpIX production and mitochondrial content of the cell, following ALA administration. However, total cell area shows positive correlation with PpIX production. Administration of the iron chelator, 1,2-dimethyl-3-hydroxy-4- pyridone (LI) in combination with ALA allows the final step in the heme synthesis pathway, conversion of PpIX to heme, to be delayed and thus increases the detectable amount of PpIX in each cell line. The cell lines that have the lowest PpIX production following administration of ALA alone show the largest increase in production following the combined administration of ALA and LI. PpIX fluorescence is thought to be a measure of cellular activity and the goal of the current study was to determine which cell lines would be the most promising targets for fluorescence detection or monitoring response to therapy. The results indicate that the cells with larger size and larger numbers of mitochondria may be good potential targets for this therapy. While this conclusion may appear obvious, it is not universally true, and cellular specific variations exist which are still not fully understood.

Original languageEnglish (US)
Title of host publicationOptical Methods for Tumor Treatment and Detection
Subtitle of host publicationMechanisms and Techniques in Photodynamic Therapy XV
DOIs
StatePublished - Jun 30 2006
Externally publishedYes
EventOptical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XV - San Jose, CA, United States
Duration: Jan 21 2006Jan 22 2006

Publication series

NameProgress in Biomedical Optics and Imaging - Proceedings of SPIE
Volume6139
ISSN (Print)1605-7422

Other

OtherOptical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XV
CountryUnited States
CitySan Jose, CA
Period1/21/061/22/06

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Biomaterials
  • Atomic and Molecular Physics, and Optics
  • Radiology Nuclear Medicine and imaging

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  • Cite this

    Gibbs, S. L., Chen, B., Ohara, J. A., Jack Hoopes, P., Hasan, T., & Pogue, B. W. (2006). Analysis of cell line variation in biochemical production of protoporphyrin IX. In Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XV [61390A] (Progress in Biomedical Optics and Imaging - Proceedings of SPIE; Vol. 6139). https://doi.org/10.1117/12.644787