RRC ID 64104
著者 Hagiya Y, Adachi T, Ogura S, An R, Tamura A, Nakagawa H, Okura I, Mochizuki T, Ishikawa T.
タイトル 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.
ジャーナル J Exp Ther Oncol
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.
巻・号 7(2)
ページ 153-67
公開日 2008-1-1
PMID 18771089
MeSH ATP Binding Cassette Transporter, Subfamily G, Member 2 ATP-Binding Cassette Transporters / biosynthesis* ATP-Binding Cassette Transporters / genetics Aminolevulinic Acid / pharmacology Benzothiazoles Blotting, Western Cell Line, Tumor Chlorophyll / analogs & derivatives Chlorophyll / pharmacology Chromatography, High Pressure Liquid Diamines Electrophoresis, Polyacrylamide Gel Fluorescent Dyes Heme Oxygenase-1 / biosynthesis* Heme Oxygenase-1 / genetics Humans NF-E2-Related Factor 2 / genetics NF-E2-Related Factor 2 / physiology* Neoplasm Proteins / biosynthesis* Neoplasm Proteins / genetics Neoplasms / pathology Neoplasms / therapy* Organic Chemicals Oxidative Stress Photochemistry Photochemotherapy* Photosensitizing Agents / pharmacology Porphyrins / chemistry* Porphyrins / radiation effects* Protoporphyrins / pharmacology Quinolines RNA, Messenger / biosynthesis RNA, Messenger / genetics RNA, Small Interfering / pharmacology Transfection
リソース情報
ヒト・動物細胞 Hep G2(RCB1648)