ABCG2-mediated transport of photosensitizers: Potential impact on photodynamic therapy

Robey, Robert W.; Steadman, Kenneth; Polgar, Orsolya; Bates, Susan E.

doi:10.4161/cbt.4.2.1440

Cited by 204Drug Transport and Resistance MechanismsPhotodynamic Therapy Research StudiesNanoplatforms for cancer theranostics

ABCG2-mediated transport of photosensitizers: Potential impact on photodynamic therapy

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Robey, Robert W., Steadman, Kenneth, Polgar, Orsolya, Bates, Susan E.·2005·Cancer Biology & Therapy

DOI 10.4161/cbt.4.2.1440

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Abstract

In photodynamic therapy (PDT), a tumor-selective photosensitizer is administered followed by activation of the photosensitizer by exposure to a light source of a given wavelength. This, in turn, generates reactive oxygen species that induce cellular apoptosis and necrosis in tumor tissue. Based on our earlier finding that the photosensitizer pheophorbide a is an ABCG2 substrate, we explored the ability of ABCG2 to transport photosensitizers with a structure similar to that of pheophorbide a. ABCG2-overexpressing NCI-H1650 MX50 bronchoalveolar carcinoma cells were found to have reduced intracellular accumulation of pyropheophorbide a methyl ester and chlorin e6 compared to parental cells as measured by flow cytometry. The ABCG2 inhibitor fumitremorgin C was found to abrogate ABCG2-mediated transport. Intracellular fluorescence of hematoporphyrin IX, meso-tetra(3-hydroxyphenyl)porphyrin, and meso-tetra(3-hydroxyphenyl)chlorin was not substantially affected by ABCG2. ABCG2-overexpressing cells also displayed decreased intracellular fluorescence of protoporphyrin IX generated by exogenous application of 5-aminolevulinic acid. Mutations at amino acid 482 in the ABCG2 protein known to affect substrate specificity were not found to impact transport of the photosensitizers. In cytotoxicity assays, ABCG2-transfected HEK-293 cells were 11-fold, 30-fold, 4-fold, and >7-fold resistant to PDT with pheophorbide a, pyropheophorbide a methyl ester, chlorin e6, and 5-aminolevulinic acid, respectively. ABCG2-transfected cells were not resistant to PDT with meso-tetra(3-hydroxyphenyl) chlorin. Neither multidrug resistance-associated protein 1 expression nor P-glycoprotein expression appreciably decreased the intracellular fluorescence of any of the photosensitizers examined as determined by flow cytometry. The results presented here implicate ABCG2 as a possible cause for cellular resistance to photodynamic therapy.

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FTC is the first selective ABCG2 inhibitor shown to significantly increase ALA-PpIX fluorescence and PDT-induced cytotoxicity in ABCG2-transfected cells.
“Fumitremorgin C (FTC) is the first selective ABCG2 inhibitor shown to significantly increase ALA-PpIX fluorescence and PDT-induced cytotoxicity in ABCG2-transfected cells [120].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [120]

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Authors: Robey, R. W., Steadman, K., Polgar, O., & Bates, S. E.
Affiliations: National Institutes of Health (US)
Corresponding author: Robey, Robert W.
ORCID: Robey, Robert W.
Steadman, Kenneth
Bates, Susan E.
Venue: Cancer Biology & Therapy
Publisher: Informa UK Limited
Published: 2005-02-02
Volume: 4
Issue: 2
Pages: 195-202
ISSN: 1538-4047 (ISSN-L)
1555-8576
DOI: 10.4161/cbt.4.2.1440
OpenAlex: W1969092519
Cited by: 204
References: 0
Citations by year: 2026: 4 · 2025: 4 · 2024: 9 · 2023: 8 · 2022: 6 · 2021: 10 · 2020: 8 · 2019: 8 · 2018: 12 · 2017: 17 · 2016: 9 · 2015: 18 · 2014: 18 · 2013: 11 · 2012: 10
FWCI: 4.06
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Cancer Biology & Therapy (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute
Topics: Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
Keywords: ABCG2, photodynamic therapy, pheophorbide a, chlorin e6, hematoporphyrin IX, protoporphyrin IX, 5-aminolevulinic acid, fumitremorgin C, ABCG2 inhibitors, multidrug resistance, P-glycoprotein, porphyrin accumulation, PDT resistance, bronchioloalveolar carcinoma
MeSH terms: ATP Binding Cassette Transporter, Subfamily G, Member 2, Aminolevulinic Acid, Biological Transport, Adenocarcinoma, Bronchiolo-Alveolar, Chlorophyll, Chlorophyllides, Flow Cytometry, Fluorescence, Humans, Indoles, Kidney, Lung Neoplasms, Neoplasm Proteins, Photochemotherapy, Porphyrins, Protoporphyrins, Tumor Cells, Cultured, Photosensitizing Agents, ATP-Binding Cassette Transporters, ATP Binding Cassette Transporter, Subfamily B, Member 1, ATP-Binding Cassette, Sub-Family C Proteins, Multidrug Resistance-Associated Proteins, Cell Proliferation

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ABCG2-mediated transport of photosensitizers: Potential impact on photodynamic therapy

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