Open AccessJournal Article
Nrf2-dependent induction of human ABC transporter ABCG2 and heme oxygenase-1 in HepG2 cells by photoactivation of porphyrins: biochemical implications for cancer cell response to photodynamic therapy.
Yuichiro Hagiya,Tatsuhiko Adachi,Shun-ichiro Ogura,Ran An,Ai Tamura,Hiroshi Nakagawa,Ichiro Okura,Tohru Mochizuki,Toshihisa Ishikawa +8 more
TLDR
Nrf2-specific siRNA treatments suppressed the induction of both ABCG2 and HO-1 after the photoactivation of porphyrins, suggesting that Nrf2 is a common regulator for transcriptional activation of the ABCG two genes in cancer cells.Abstract:
Photodynamic therapy is a recently developed anticancer treatment that utilizes the generation of singlet oxygen and other reactive oxygen species in cancer tissue. Nrf2, an NF-E2-related transcription factor, plays a pivotal role in transcriptional upregulation of many target genes, including those for metabolizing enzymes and transporters essential for cellular defense in response to oxidative stress. In the present study, we examined the potential involvement of Nrf2 in the induction of human ABC transporter ABCG2 and heme oxygenase-1 (HO-1). When HepG2 cells were incubated with non-toxic concentrations of delta-aminolevulinic acid, protoporphyrin IX, or pheophorbide a and then exposed to visible light for 90 min, the mRNA level of HO-1 began increasing markedly, reaching the maximal level in 4 h. Following the transient induction of HO-1, the mRNA level of ABCG2 gradually increased in a time-dependent manner, whereas the ABCB6 mRNA level was little affected. Nrf2-specific siRNA treatments suppressed the induction of both ABCG2 and HO-1 after the photoactivation of porphyrins, suggesting that Nrf2 is a common regulator for transcriptional activation of the ABCG2 and HO-1 genes. On the other hand, the mRNA level of HO-1 was remarkably enhanced by Zn(2+)-protoporphyrin IX or hemin even in the absence of light. This induction may be attributed to inactivation of Bach1, a repressor for the HO-1 gene, by those compounds. Since patients have demonstrated individual defferences in their response to photodynamic therapy, transcriptional activation of the ABCG2 and HO-1 genes in cancer cells may affect patients' responses to photodynamic therapy.read more
Citations
More filters
Journal ArticleDOI
Nrf2 is overexpressed in pancreatic cancer: implications for cell proliferation and therapy
Adam Lister,Taoufik Nedjadi,Neil R. Kitteringham,Fiona Campbell,Eithne Costello,Bryony H. Lloyd,Ian M. Copple,Samantha J. Williams,Andrew Owen,John P. Neoptolemos,Christopher E. Goldring,B. Kevin Park +11 more
TL;DR: Expression of Nrf2 is up-regulated in pancreatic cancer cell lines and ductal adenocarcinomas, which may reflect a greater intrinsic capacity of these cells to respond to stress signals and resist chemotherapeutic interventions.
Journal ArticleDOI
Novel development of 5-aminolevurinic acid (ALA) in cancer diagnoses and therapy
Masahiro Ishizuka,Fuminori Abe,Yuki Sano,Kiwamu Takahashi,Katsushi Inoue,Motowo Nakajima,Takeo Kohda,Naoki Komatsu,Shun-ichiro Ogura,Tohru Tanaka +9 more
TL;DR: The biological significance of heme metabolites, the mechanism of PpIX accumulation in tumor cells, and the therapeutic potential of ALA-induced PDT alone and combined with hyperthermia and immunotherapy are discussed.
Journal ArticleDOI
Cell death in photodynamic therapy: From oxidative stress to anti-tumor immunity.
TL;DR: The investigation of the mechanisms of cell death under the oxidative stress of PDT is of paramount importance to understand how the immune system is activated and, ultimately, to make PDT a more appealing/relevant therapeutic option.
Journal ArticleDOI
Tumor cell survival pathways activated by photodynamic therapy: a molecular basis for pharmacological inhibition strategies
Mans Broekgaarden,Ruud Weijer,Thomas M. van Gulik,Michael R. Hamblin,Michael R. Hamblin,Michal Heger +5 more
TL;DR: In this paper, the molecular mechanisms are elucidated that occur post-PDT to mediate cancer cell survival, on the basis of which pharmacological interventions are proposed, specifically, pharmaceutical inhibitors of the molecular regulators of each survival pathway are addressed.
Journal ArticleDOI
Pivotal roles of peptide transporter PEPT1 and ATP-binding cassette (ABC) transporter ABCG2 in 5-aminolevulinic acid (ALA)-based photocytotoxicity of gastric cancer cells in vitro
Yuichiro Hagiya,Yoshio Endo,Yutaka Yonemura,Kiwamu Takahashi,Masahiro Ishizuka,Fuminori Abe,Tohru Tanaka,Ichiro Okura,Motowo Nakajima,Toshihisa Ishikawa,Shun-ichiro Ogura +10 more
TL;DR: PEPT1 and ABCG2 are key players in regulating intracellular PpIX levels and determining the efficacy of ALA-based photocytotoxicity against gastric cancer cells in vitro.