Photodynamic therapy mediated induction of early response genes

• Published in: Cancer research (Chicago, Ill.) Vol. 54; no. 5; pp. 1374 - 1380
• Main Authors: LUNA, M. C, WONG, S, GOMER, C. J
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-03-1994
• Subjects: Animals; Biological and medical sciences; Drug Interactions; Fibrosarcoma - drug therapy; Fibrosarcoma - genetics; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - physiology; Genes, fos - genetics; Genes, Immediate-Early - drug effects; Genes, Immediate-Early - genetics; Medical sciences; Mice; Phospholipases - antagonists & inhibitors; Photochemotherapy; Photoradiation therapy and photosensitizing agent; Photosensitizing Agents - pharmacology; Promoter Regions, Genetic - drug effects; Promoter Regions, Genetic - genetics; Protein Kinase Inhibitors; Reactive Oxygen Species - toxicity; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stress, Physiological - chemically induced; Stress, Physiological - physiopathology; Transcription, Genetic - drug effects; Transcription, Genetic - genetics; Treatment with physical agents; Treatment. General aspects; Tumors; Rodentia; Activation; Gene expression; In vitro; Phototherapy; Vertebrata; Mammalia; Treatment; Mouse; Animal; Established cell line; Mechanism of action; Photosensitizer; Tumor cell; Immediate early gene
• ISSN: 0008-5472; 1538-7445

Photodynamic therapy (PDT) generates reactive oxygen species which initiate the cytotoxic events of this tumor treatment. We demonstrate that PDT mediated oxidative stress induced a transient increase in the early response genes c-fos, c-jun, c-myc, and egr-1 in murine radiation-induced fibrosarcoma cells. Incubation of exponentially growing cells with porphyrin based photosensitizers in the dark also induced an increase in mRNA levels of early response genes. However, the xanthine photosensitizer, rose bengal, produced increased c-fos mRNA levels only following light treatment. Nuclear runoff experiments confirmed that the induction of c-fos mRNA is controlled in part at the level of transcription. Likewise, a chloramphenicol acetyltransferase reporter construct containing the major c-fos transcriptional response elements was inducible by porphyrin and PDT. Signal transduction pathways associated with PDT mediated c-fos activation were examined by treating cells with protein kinase inhibitors. Staurosporine and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine inhibited PDT mediated c-fos activation while N-(2-guanidinoethyl)-5-isoquinoline-sulfonamide had no effect. In addition, quinacrine, which can inhibit phospholipase activity, blocked PDT induced c-fos mRNA expression. These results suggest that photosensitizer mediated oxidative stress acts through protein kinase-mediated signal transduction pathway(s) to activate early response genes.