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

Ishikawa, Toshihisa; Kajimoto, Yoshinaga; Sun, Wei; Nakagawa, Hiroshi; Inoue, Yutaka; Ikegami, Yoji; Miyatake, Shin‐Ichi; Kuroiwa, Toshihiko

doi:10.1002/jps.23563

Cited by 34 publications

(13 citation statements)

References 94 publications

(114 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To elucidate the mechanisms regulating ABCG2 expression in injured tissues, several groups have attempted to analyse the promoter region of Abcg2 . The hypoxia‐response element and antioxidant responsive element, which are recognized by HIF‐1 complex and Nrf2, respectively , were found within the cis‐active element upstream of the ABCG2 coding region. HIF‐1 was reported to be stabilized in response to tissue inflammation resulting from injury and failure of HIF‐1 α stabilization leading to impaired wound healing was reported in diabetic wounds .…”

Section: Discussionmentioning

confidence: 99%

ABCG2 deficiency in skin impairs re‐epithelialization in cutaneous wound healing

Chang

Huang

Lin

et al. 2016

Experimental Dermatology

View full text Add to dashboard Cite

The ATP-binding cassette transporter ABCG2 is expressed in the interfollicular epidermis and mediates the side-population phenotype in skin cells. However, the role of ABCG2 in skin is unclear. Increased expression levels of ABCG2 were found at the basal layer of transitional epidermis adjacent to cutaneous wounds in human patients, indicating that ABCG2 may be involved in regulating the wound healing process. To investigate the role of ABCG2 in cutaneous wound healing, full-thickness skin wounds were created in ABCG2 knockout (ABCG2-KO) and wild-type mice. The healing process was analysed and revealed that ABCG2 deficiency in skin results in delays in wound closure and impairments in re-epithelialization, as evidenced by reductions in both suprabasal differentiation and in p63-expressing keratinocytes migrating from transitional epidermis to epithelial tongues. The reduction in p63-expressing cells may be due to elevated levels of reactive oxygen species in ABCG2-KO epidermis, which can cause DNA damage and lead to proliferation arrest. To determine whether ABCG2 deficiency affects the potency of epidermal stem/progenitor cells (EPCs), transplantation studies were carried out, which demonstrated that ABCG2-KO EPCs display higher levels of γH2AX and lose the capacity to differentiate into suprabasal keratinocytes. A competitive repopulation assay confirmed that ABCG2 expression is critical for the proper expansion and differentiation of EPCs in cutaneous wounds. As EPCs are known to contribute to the healing of larger wounds, the current findings imply a functional role for ABCG2 in the expansion and differentiation of p63-expressing EPCs. Thus, ABCG2 deficiency in skin impairs re-epithelialization in cutaneous wound healing.

show abstract

Section: Discussionmentioning

confidence: 99%

ABCG2 deficiency in skin impairs re‐epithelialization in cutaneous wound healing

Chang

Huang

Lin

et al. 2016

Experimental Dermatology

View full text Add to dashboard Cite

show abstract

“…As ABCG2 expression determines the PpIX level in cells, taking advantage of suppressing ABCG2 expression and thereby promoting PDT efficiency could be feasible. Based on a former study by Ishikawa et al [ 38 ], we used gefitinib, curcumin, and EGCG to inhibit ABCG2 expression in HNC cells. As gefitinib, EGCG, and curcumin inhibited ABCG2 expression, although to varying degrees, reducing intracellular PpIX accumulation and increasing oral cancer cell viability, these results suggest that there might be a possible benefit of treating early-stage oral cancer patients with PDT in combination with EGCG or curcumin to enhance treatment effectiveness in a future medication plan.…”

Section: Discussionmentioning

confidence: 99%

Natural Compounds Modulate Drug Transporter Mediated Oral Cancer Treatment

Yang

Wei

Li³

et al. 2020

Biomolecules

View full text Add to dashboard Cite

Oral cancer (OC) is a serious health problem. Surgery is the best method to treat the disease but might reduce the quality of life of patients. Photodynamic therapy (PDT) may enhance quality of life but with some limitations. Therefore, the development of a new strategy to facilitate PDT effectiveness has become crucial. ATP-binding cassette G2 (ABCG2) is a membrane protein-associated drug resistance and stemness in cancers. Here, we examined whether ABCG2 plays an important role in regulating the treatment efficacy of PDT and whether ABCG2 inhibition by natural compounds can promote the effect of PDT in OC cells. Several head and neck cancer cells were utilized in this study. OECM1 and SAS cells were selected to investigate the relationship between ABCG2 expression and protoporphyrin IX (PpIX) accumulation. Western blot analysis, flow cytometry analysis, and survival probability were performed to determine PDT efficacy and cellular stemness upon treatment of different dietary compounds, including epigallocatechin gallate (EGCG) and curcumin. In this study, we found that ABCG2 expression varied in OC cells. Hypoglycemic culture for SAS cells enhanced ABCG2 expression as higher ABCG2 expression was associated with lower PpIX accumulation and cellular stemness in OC cells. In contrast, suppression of ABCG2 expression by curcumin and tea polyphenol EGCG led to greater PpIX accumulation and enhanced PDT treatment efficiency in OC cells. In conclusion, ABCG2 plays an important role in regulating the effect of PDT. Change in glucose concentration and treatment with natural compounds modulated ABCG2 expression, resulting in altered PDT efficacy for OC cells. These modulations raise a potential new treatment strategy for early-stage OCs.

show abstract

“…Zong et al (2006) showed multiple transcription start sites from several leader exons in abcg2 gene. Moreover, these promoter regions are enriched with several transcription factors binding sites (Ishikawa et al, 2013). Furthermore, abcg2 promoter is regulated by tissue specific transcription factors such as GATA 2 (Minegishi et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Expression of ABCG2 (BCRP) in mouse models with enhanced erythropoiesis

Latunde-Dada¹,

Laftah²,

Masaratana³

et al. 2014

Front. Pharmacol.

View full text Add to dashboard Cite

Haem is a structural component of numerous cellular proteins which contributes significantly to iron metabolic processes in mammals but its toxicity demands that cellular levels must be tightly regulated. Breast Cancer Resistance Protein (BCRP/ABCG2), an ATP Binding Cassette G-member protein has been shown to possess porphyrin/haem efflux function. The current study evaluated the expression and regulation of Abcg2 mRNA and protein levels in mouse tissues involved in erythropoiesis. Abcg2 mRNA expression was enhanced in bone marrow hemopoietic progenitor cells from mice that were treated with phenylhydrazine (PHZ). Abcg2 mRNA expression was increased particularly in the extramedullary haematopoietic tissues from all the mice models with enhanced erythropoiesis. Haem oxygenase (ho1) levels tended to increase in the liver of mice with enhanced erythropoiesis and gene expression patterns differed from those observed in the spleen. Efflux of haem biosynthetic metabolites might be dependent on the relative abundance of Abcg2 or ho1 during erythropoiesis. Abcg2 appears to act principally as a safety valve regulating porphyrin levels during the early stages of erythropoiesis and its role in systemic haem metabolism and erythrophagocytosis, in particular, awaits further clarification.

show abstract

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

Cited by 34 publications

References 94 publications

ABCG2 deficiency in skin impairs re‐epithelialization in cutaneous wound healing

ABCG2 deficiency in skin impairs re‐epithelialization in cutaneous wound healing

Natural Compounds Modulate Drug Transporter Mediated Oral Cancer Treatment

Expression of ABCG2 (BCRP) in mouse models with enhanced erythropoiesis

Contact Info

Product

Resources

About