Abstract
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.
Highlights
Photodynamic therapy (PDT) and photodynamic diagnosis are achieved by a photon-induced physicochemical reaction which is induced by excitation of photosensitizer exposed to light
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
We have reported that cellular phototoxicity was evoked through the inhibition of human ABC transporter ABCG2 by imatinib [42] and cyclin-dependent kinase (CDK) inhibitors [43]
Summary
Photodynamic therapy (PDT) and photodynamic diagnosis are achieved by a photon-induced physicochemical reaction which is induced by excitation of photosensitizer exposed to light. In the 1960s Lipson and Baldes introduced a hematoporphyrin derivative (HpD), a product derived following by treatment of hematoporphyrin with a mixture of acetic and sulfuric acids and sodium hydroxide [1] Their development of the hematoporphyrin derivative established the basis of today’s PDT and photodynamic diagnosis [2,3,4,5,6]. Advances in Pharmacological Sciences to PpIX which is fluorescent This phenomenon has been clinically applied to the detection of neoplasms in the brain and other organs, such as the bladder, skin, and bronchus. This technique is generally termed fluorescence diagnosis or photodynamic diagnosis. HepG2, a human hepatocarcinoma cell line, has been enzymatically well characterized to synthesize PpIX endogenously from exogenous ALA [29]
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