Drug-induced phototoxicity evoked by inhibition of human ABC transporter ABCG2: development of<i>in vitro</i>high-speed screening systems

Tamura, Ai; An, Ran; Hagiya, Yuichiro; Hoshijima, Kazuyuki; Yoshida, Takashi; Mikuriya, Kenta; Ishikawa, Toshihisa

doi:10.1517/17425255.4.3.255

Cited by 18 publications

(10 citation statements)

References 114 publications

(128 reference statements)

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“…9,39 Tamura and colleagues proved an in vitro evaluation of photosensitivity risk related to genetic polymorphisms of human ATP-binding cassette (ABC) transporter ABCG and inhibition by drugs demonstrating an inhibition by imatinib on the ATPbinding cassette subfamily G member 2 (ABCG2)-mediated porphyrin transport with a significant enhancement of the cellular photosensitivity. 40,41 We may hypothesize that certain genetic polymorphisms and/or inhibition of ABCG2 by imatinib can enhance the potential risk of photosensitivity. At the same time, imatinib impairs melanogenesis via its inhibition of c-Kit activity, thereby altering the skin's protection against ultraviolet ray exposure.…”

Section: Imatinib Mesylatementioning

confidence: 99%

Imatinib, dasatinib and nilotinib: a review of adverse cutaneous reactions with emphasis on our clinical experience

Brazzelli

Grasso

Borroni

2013

Acad Dermatol Venereol

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In the last years, several tyrosine kinase inhibitors (TKIs) have been developed and approved for human cancer treatment. Imatinib mesylate was the first of this novel family of drugs that target cancer-specific molecules and signalling pathways. The appearance of imatinib resistances led to the introduction of second-generation TKIs with higher potency and selectivity, such as dasatinib and nilotinib. However, the range of activity of these agents is not simply directed at tumour cells. Patients and their clinicians are indeed frequently confronted with the cutaneous side-effects associated with the employ of these drugs, which represent the most common non-hematological adverse reactions. For this reason, a systematic dermatological survey of patients receiving these therapies is highly important, and an early and appropriate dermatological treatment is required. In this review, we analyse the clinical and pathological characteristics of the most commonly reported adverse skin events associated with first- and second-generation tyrosine kinase inhibitors, with a particular emphasis on our clinical experience.

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Section: Imatinib Mesylatementioning

confidence: 99%

Imatinib, dasatinib and nilotinib: a review of adverse cutaneous reactions with emphasis on our clinical experience

Brazzelli

Grasso

Borroni

2013

Acad Dermatol Venereol

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“…This assay takes advantage of the fact that porphyrins have a unique absorption and emission wavelength that makes it amenable to high-throughput screening by fluorescence-activated cell sorting [41]. This screening assay can help not only to identity new Abcg2 inhibitors for therapy but also to eliminate molecules that could lead to disruption of porphyrin homeostasis.…”

Section: Pathologic Implicationsmentioning

confidence: 99%

The Role of ABCG2 and ABCB6 in Porphyrin Metabolism and Cell Survival

Krishnamurthy

Schuetz²

2011

CPB

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The porphyrins (such as heme) are essential molecules within cells and have multiple roles in essential cellular processes such as: the mitochondrial electron transport chain, free-radical detoxification, and metabolism. The porphyrins need energy to traverse biological membranes. Our understanding of ABC transporters role in regulating intracellular porphyrin homeostasis is only now beginning to be understood. Two important contributors are members of the ABC transporter gene family: ABCB6 and ABCG2. ABCB6 is the first ABC transporter located in the outer mitochondrial membrane and oriented to facilitate porphyrin import. Consequently, ABCB6 can regulate and appropriately orchestrate porphyrin synthesis. This leads to an ability to regulate the amount of heme associated with heme requiring proteins. This ability can facilitate a cells protective response to an array of toxic insults. ABCG2 also binds and transports porphyrins, however its location at the plasma membrane provides a mechanism to remove excess porphyrins. Because ABCG2 is upregulated by hypoxia this provides a mechanism to export porphyrins, rebalance porphyrins and protect cells from porphyrin overaccumulation. Such a mechanism would be important to hypoxic cells which exhibit an increase in porphyrin synthesis under hypoxic conditions. Finally, we propose that these two transporters (ABCB6 and ABCG2) are coordinately regulated to modulate porphyrin concentrations under normal physiological and pathological conditions.

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“…Accumulating evidence suggests that ABCG2 is responsible for the cellular homeostasis of porphyrins and their related compounds 14–16. Hitherto, evidence has been accumulating to show that ABCG2 transports porphyrins in an ATP‐dependent manner 17–19. Furthermore, Robey et al20 reported that ABCG2‐mediated transport of photosensitizers has a potential impact on PDT.…”

Section: Introductionmentioning

confidence: 99%

Role of Nrf2 in Cancer Photodynamic Therapy: Regulation of Human ABC Transporter ABCG2

Ishikawa¹,

Kajimoto

Sun

et al. 2013

Journal of Pharmaceutical Sciences

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

Cited by 18 publications

References 114 publications

Imatinib, dasatinib and nilotinib: a review of adverse cutaneous reactions with emphasis on our clinical experience

Imatinib, dasatinib and nilotinib: a review of adverse cutaneous reactions with emphasis on our clinical experience

The Role of ABCG2 and ABCB6 in Porphyrin Metabolism and Cell Survival

Role of Nrf2 in Cancer Photodynamic Therapy: Regulation of Human ABC Transporter ABCG2

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