Past and Future: Porphyria and Porphyrins

Norman, Robert A.

doi:10.1111/j.1540-9740.2005.03706.x

Cited by 19 publications

(11 citation statements)

References 35 publications

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“…ABCB6, one of human ABC transporters, reportedly transports coproporphyrinogen III from the cytoplasm to the mitochondria [19], whereas another ABC transporter ABCG2 is responsible for the cellular homeostasis of porphyrins and their related compounds [20]. Disturbances in cellular heme biosynthesis or metabolism are associated with several types of porphyria, which represent an elevation of toxic hemeprecursors, for example, protoporphyrins [21–23]. …”

Section: Biosynthesis and Metabolism Of Porphyrins And Hemementioning

confidence: 99%

Key Role of Human ABC Transporter ABCG2 in Photodynamic Therapy and Photodynamic Diagnosis

Ishikawa

Nakagawa

Hagiya

et al. 2010

Advances in Pharmacological Sciences

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Accumulating evidence indicates that ATP-binding cassette (ABC) transporter ABCG2 plays a key role in regulating the cellular accumulation of porphyrin derivatives in cancer cells and thereby affects the efficacy of photodynamic therapy and photodynamic diagnosis. The activity of porphyrin efflux can be affected by genetic polymorphisms in the ABCG2 gene. On the other hand, Nrf2, an NF-E2-related transcription factor, has been shown to be involved in oxidative stress-mediated induction of the ABCG2 gene. Since patients have demonstrated individual differences in their response to photodynamic therapy, transcriptional activation and/or genetic polymorphisms of the ABCG2 gene in cancer cells may affect patients' responses to photodynamic therapy. Protein kinase inhibitors, including imatinib mesylate and gefitinib, are suggested to potentially enhance the efficacy of photodynamic therapy by blocking ABCG2-mediated porphyrin efflux from cancer cells. This review article provides an overview on the role of human ABC transporter ABCG2 in photodynamic therapy and photodynamic diagnosis.

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Section: Biosynthesis and Metabolism Of Porphyrins And Hemementioning

confidence: 99%

Key Role of Human ABC Transporter ABCG2 in Photodynamic Therapy and Photodynamic Diagnosis

Ishikawa

Nakagawa

Hagiya

et al. 2010

Advances in Pharmacological Sciences

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“…The Abcg2-knockout mice study suggests that photosensitivity can be evoked as a synergetic consequence of both genetic disorder and environmental factors. Porphyria is recognized as a peculiar group of genetic disorders resulting from hereditary or acquired deficiencies in the biosynthetic pathway of hemes [74] . Depending on the site of heme-biosynthetic enzyme defect, porphyrias are classified as being erythropoietic or hepatic.…”

Section: Porphyrin Biosynthesis and Transportmentioning

confidence: 99%

Drug-induced phototoxicity evoked by inhibition of human ABC transporter ABCG2: development ofin vitrohigh-speed screening systems

Tamura

Hagiya

et al. 2008

Expert Opinion on Drug Metabolism & Toxicology

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Background : Photosensitivity depends on both genetic and environmental factors. Pheophorbide a, present in various plant-derived foods and food supplements, can be absorbed by the small intestine. Accumulation of pheophorbide a and porphyrins in the systemic blood circulation can result in phototoxic lesions on light-exposed skin. Objective : As the human ATP-binding cassette (ABC) transporter ABCG2 has been suggested to be critically involved in porphyrin-mediated photosensitivity, we aimed to develop in vitro screening systems for drug-induced phototoxicity. Conclusion : Functional impairment owing to inhibition of ABCG2 by drugs or its genetic polymorphisms can lead to the disruption of porphyrin homeostasis. This review article provides an overview on drug-induced photosensitivity, as well as our hypothesis on a potential role of ABCG2 in phototoxicity.

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“…ABCB6, one of human ABC transporters, reportedly transports coproporphyrinogen III from the cytoplasm to the mitochondria [19], whereas another ABC transporter ABCG2 is responsible for the cellular homeostasis of porphyrins and their related compounds [20]. Disturbances in cellular porphyrin biosynthesis or metabolism are associated with several types of porphyria, which represent an elevation of photo-toxic hemeprecursors including PpIX [21-23]. …”

Section: Biosynthesis and Metabolism Of Porphyrins And Hemementioning

confidence: 99%

Transporter-Mediated Drug Interaction Strategy for 5-Aminolevulinic Acid (ALA)-Based Photodynamic Diagnosis of Malignant Brain Tumor: Molecular Design of ABCG2 Inhibitors

et al. 2011

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Photodynamic diagnosis (PDD) is a practical tool currently used in surgical operation of aggressive brain tumors, such as glioblastoma. PDD is achieved by a photon-induced physicochemical reaction which is induced by excitation of protoporphyrin IX (PpIX) exposed to light. Fluorescence-guided gross-total resection has recently been developed in PDD, where 5-aminolevulinic acid (ALA) or its ester is administered as the precursor of PpIX. ALA induces the accumulation of PpIX, a natural photo-sensitizer, in cancer cells. Recent studies provide evidence that adenosine triphosphate (ATP)-binding cassette (ABC) transporter ABCG2 plays a pivotal role in regulating the cellular accumulation of porphyrins in cancer cells and thereby affects the efficacy of PDD. Protein kinase inhibitors are suggested to potentially enhance the PDD efficacy by blocking ABCG2-mediated porphyrin efflux from cancer cells. It is of great interest to develop potent ABCG2-inhibitors that can be applied to PDD for brain tumor therapy. This review article addresses a pivotal role of human ABC transporter ABCG2 in PDD as well as a new approach of quantitative structure-activity relationship (QSAR) analysis to design potent ABCG2-inhibitors.

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Past and Future: Porphyria and Porphyrins

Cited by 19 publications

References 35 publications

Key Role of Human ABC Transporter ABCG2 in Photodynamic Therapy and Photodynamic Diagnosis

Key Role of Human ABC Transporter ABCG2 in Photodynamic Therapy and Photodynamic Diagnosis

Drug-induced phototoxicity evoked by inhibition of human ABC transporter ABCG2: development ofin vitrohigh-speed screening systems

Transporter-Mediated Drug Interaction Strategy for 5-Aminolevulinic Acid (ALA)-Based Photodynamic Diagnosis of Malignant Brain Tumor: Molecular Design of ABCG2 Inhibitors

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