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

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

doi:10.4161/cbt.4.2.1440

Cited by 188 publications

(168 citation statements)

References 33 publications

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“…Robey et al reported that the expression of atP-binding cassette (aBc) transport proteins, which render tumor cells resistant to chemotherapeutic drugs, decreases the accumulation of photosensitizers and causes resistance to PDt (41). We have also previously reported that BcrP, a member of the aBc transporter family, decreases the accumulation of Photofrin and may be a molecular determinant (29).…”

Section: Discussionmentioning

confidence: 99%

Combination effect of photodynamic therapy using NPe6 with pemetrexed for human malignant pleural mesothelioma cells

Maehara

Usuda

Ishizumi

et al. 2014

International Journal of Oncology

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Abstract. to identify a possible new treatment modality for malignant pleural mesothelioma (MPM), we examined whether combination treatment consisting of pemetrexed chemotherapy and photodynamic therapy (PDt) using the photosensitizer nPe6, enhanced the antitumor effect in both in vitro and in vivo models. We also investigated preclinical treatment schedules. four human malignant mesothelioma cell lines (MSto-211H, H2052, H2452 and H28) were assayed using the WSt assay after treatment with pemetrexed and nPe6-PDt. the treatment schedule for the combination treatment was examined using nude mice. Pemetrexed pre-treatment enhanced the lethal effect of nPe6-PDt in the four malignant mesothelioma cell lines, but nPe6-PDt followed by pemetrexed treatment did not enhance cell lethality in the in vitro assay. Pemetrexed pre-treatment did not enhance the intracellular accumulation of nPe6, which is one of the determinants of the antitumor effect of PDt. in nude mice injected with MSto-211H cells and then treated using a combination of pemetrexed and nPe6-PDt (10 mg/kg nPe6, 10 j/cm 2 laser irradiation), the tumor volume decreased by 50% but subsequently increased, reaching the pre-treatment value after 14 days. Pemetrexed treatment followed by nPe6-PDt resulted in an 80% reduction in the tumor size and inhibited re-growth. nPe6-PDt followed by pemetrexed treatment resulted in a 60% reduction in tumor size but did not inhibit re-growth. nPe6-PDt induced the expression of thymidylate synthase (tS), which confers resistance to pemetrexed, and nPe6-PDt followed by pemetrexed treatment did not enhance the treatment outcome in vivo. in conclusion, combination treatment, consisting of pemetrexed followed by nPe6-PDt, should be further investigated as a new treatment modality for MPM. in the future, this combination treatment may contribute to a reduction in local recurrence and a prolonged survival period in patients with MPM.

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Section: Discussionmentioning

confidence: 99%

Combination effect of photodynamic therapy using NPe6 with pemetrexed for human malignant pleural mesothelioma cells

Maehara

Usuda

Ishizumi

et al. 2014

International Journal of Oncology

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“…Notably, several TKIs such as imatinib, gefitinib, and nilotinib are BCRP substrates (1,13). A variety of photosensitizers including pheophorbide A, protoporphyrin IX, and related compounds are also BCRP substrates, suggesting that BCRP is a possible cause of cellular resistance to photodynamic therapy (14).…”

Section: Bcrp Substratesmentioning

confidence: 99%

Role of the Breast Cancer Resistance Protein (BCRP/ABCG2) in Drug Transport—an Update

Mao

Unadkat

2014

AAPS J

503

387

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Abstract. The human breast cancer resistance protein (BCRP, gene symbol ABCG2) is an ATP-binding cassette (ABC) efflux transporter. It was so named because it was initially cloned from a multidrugresistant breast cancer cell line where it was found to confer resistance to chemotherapeutic agents such as mitoxantrone and topotecan. Since its discovery in 1998, the substrates of BCRP have been rapidly expanding to include not only therapeutic agents but also physiological substances such as estrone-3-sulfate, 17β-estradiol 17-(β-D-glucuronide) and uric acid. Likewise, at least hundreds of BCRP inhibitors have been identified. Among normal human tissues, BCRP is highly expressed on the apical membranes of the placental syncytiotrophoblasts, the intestinal epithelium, the liver hepatocytes, the endothelial cells of brain microvessels, and the renal proximal tubular cells, contributing to the absorption, distribution, and elimination of drugs and endogenous compounds as well as tissue protection against xenobiotic exposure. As a result, BCRP has now been recognized by the FDA to be one of the key drug transporters involved in clinically relevant drug disposition. We published a highly-accessed review article on BCRP in 2005, and much progress has been made since then. In this review, we provide an update of current knowledge on basic biochemistry and pharmacological functions of BCRP as well as its relevance to drug resistance and drug disposition.

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“…In addition to other known porphyrin ABCG2 substrates that are used for photodynamic therapy (Robey et al, 2004(Robey et al, , 2005, we investigated Pp-18 (structure shown in Fig. 3A) as a potential new porphyrin substrate of ABCG2 by efflux studies with ABCG2-overexpressing sublines ( Fig.…”

Section: Functional Comparison Of Human and Murine Abcg2mentioning

confidence: 99%

Overlapping Substrate and Inhibitor Specificity of Human and Murine ABCG2

Bakhsheshian¹,

Hall²,

Robey³

et al. 2013

Drug Metab Dispos

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ABCG2 (also known as breast cancer resistance protein) is an ATP-binding cassette (ABC) transporter localized to the plasma membrane where it mediates the efflux of xenobiotics, including potential therapeutics. Studies investigating Abcg2 function at the blood-brain barrier in mouse models are often compared with human ABCG2 function. It is critical to understand the nature of species differences between mouse and human ABCG2, since extrapolations are made from murine data to humans. Two independent drug-selected cell line pairs expressing human or mouse ABCG2 were compared for efflux of fluorescent substrates using flow cytometry. To this end, we developed and characterized a new mouse Abcg2-expressing subline that demonstrated efflux of known fluorescent ABCG2 substrates and increased resistance to mitoxantrone, which is reduced in the presence of the ABCG2 inhibitor Ko143. Our results indicate that the substrate specificity of human and mouse ABCG2 is very similar. We identified a new human and mouse ABCG2 substrate, a porphyrin analog, purpurin-18 (Pp-18), which is not a substrate for P-glycoprotein or multidrug resistance protein 1. The ability of inhibitors to block efflux activity of ABCG2 was assessed using Pp-18. Inhibitors also demonstrated similar effects on human and mouse ABCG2. Chrysin, benzoflavone, and cyclosporin A inhibited Pp-18 efflux in both human and mouse ABCG2. The similarity of the substrate and inhibitor specificity of human and mouse ABCG2 supports interpretation of mouse models in understanding the clinical, pharmacological, and physiologic roles of ABCG2.

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

Cited by 188 publications

References 33 publications

Combination effect of photodynamic therapy using NPe6 with pemetrexed for human malignant pleural mesothelioma cells

Combination effect of photodynamic therapy using NPe6 with pemetrexed for human malignant pleural mesothelioma cells

Role of the Breast Cancer Resistance Protein (BCRP/ABCG2) in Drug Transport—an Update

Overlapping Substrate and Inhibitor Specificity of Human and Murine ABCG2

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