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- PMID: 12766487
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Article: Rapid induction of apoptosis in human keratinocytes with the photosensitizer QLT0074 via a direct mitochondrial action
Title | Rapid induction of apoptosis in human keratinocytes with the photosensitizer QLT0074 via a direct mitochondrial action |
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Authors | |
Keywords | Chemicals And Cas Registry Numbers |
Issue Date | 2003 |
Publisher | Springer New York LLC. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=1360-8185 |
Citation | Apoptosis, 2003, v. 8 n. 3, p. 269-275 How to Cite? |
Abstract | QLT0074 is a newly introduced, porphyrin-derivative for use in photodynamic therapy (PDT). In the current study, the intracellular distribution of QLT0074 and the mode of cell death induced by photosensitization with this compound in vitro were assessed for transformed human HaCaT keratinocytes. Fluorescence microscopy studies indicated a distribution of the drug to the cytoplasm, nuclear membrane and mitochondria of these cells. In the absence of light, QLT0074 produced no evidence of apoptosis-related biochemical changes or affected cell viability. When combined with blue light exposure, cytotoxicity was exerted in a QLT0074- and light-dose-related manner. Appearance of the mitochondrial protein cytochrome c in the cytosolic fraction and expression of the apoptosis-associated mitochondrial 7A6 antigen were demonstrable following photosensitization at nanomolar levels of QLT0074. Evidence of processing of the apoptosis-effector molecules caspase-3, -6, -7, -8 and -9 as well as cleavage of the caspase-3 substrate poly (ADP-ribose) polymerase (PARP) were demonstrable subsequent to cytochrome c release after PDT. Treatment with the anti-oxidant pyrrolidine dithiocarbamate (PDTC) inhibited cytochrome c release, caspase-3 activation and PARP cleavage associated with PDT thereby supporting the contention that QLT0074 induces apoptosis through the generation of reactive oxygen species upon light activation. QLT0074 is a potent photosensitizer with the capacity to directly initiate apoptosis by acting upon mitochondria. |
Persistent Identifier | http://hdl.handle.net/10722/91685 |
ISSN | 2023 Impact Factor: 6.1 2023 SCImago Journal Rankings: 1.427 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
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dc.contributor.author | Li, R | en_HK |
dc.contributor.author | Bounds, DJ | en_HK |
dc.contributor.author | Granville, D | en_HK |
dc.contributor.author | Ip, SH | en_HK |
dc.contributor.author | Jiang, H | en_HK |
dc.contributor.author | Margaron, P | en_HK |
dc.contributor.author | Hunt, DWC | en_HK |
dc.date.accessioned | 2010-09-17T10:23:19Z | - |
dc.date.available | 2010-09-17T10:23:19Z | - |
dc.date.issued | 2003 | en_HK |
dc.identifier.citation | Apoptosis, 2003, v. 8 n. 3, p. 269-275 | en_HK |
dc.identifier.issn | 1360-8185 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/91685 | - |
dc.description.abstract | QLT0074 is a newly introduced, porphyrin-derivative for use in photodynamic therapy (PDT). In the current study, the intracellular distribution of QLT0074 and the mode of cell death induced by photosensitization with this compound in vitro were assessed for transformed human HaCaT keratinocytes. Fluorescence microscopy studies indicated a distribution of the drug to the cytoplasm, nuclear membrane and mitochondria of these cells. In the absence of light, QLT0074 produced no evidence of apoptosis-related biochemical changes or affected cell viability. When combined with blue light exposure, cytotoxicity was exerted in a QLT0074- and light-dose-related manner. Appearance of the mitochondrial protein cytochrome c in the cytosolic fraction and expression of the apoptosis-associated mitochondrial 7A6 antigen were demonstrable following photosensitization at nanomolar levels of QLT0074. Evidence of processing of the apoptosis-effector molecules caspase-3, -6, -7, -8 and -9 as well as cleavage of the caspase-3 substrate poly (ADP-ribose) polymerase (PARP) were demonstrable subsequent to cytochrome c release after PDT. Treatment with the anti-oxidant pyrrolidine dithiocarbamate (PDTC) inhibited cytochrome c release, caspase-3 activation and PARP cleavage associated with PDT thereby supporting the contention that QLT0074 induces apoptosis through the generation of reactive oxygen species upon light activation. QLT0074 is a potent photosensitizer with the capacity to directly initiate apoptosis by acting upon mitochondria. | en_HK |
dc.language | eng | en_HK |
dc.publisher | Springer New York LLC. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=1360-8185 | en_HK |
dc.relation.ispartof | Apoptosis | en_HK |
dc.subject | Chemicals And Cas Registry Numbers | en_HK |
dc.title | Rapid induction of apoptosis in human keratinocytes with the photosensitizer QLT0074 via a direct mitochondrial action | en_HK |
dc.type | Article | en_HK |
dc.identifier.email | Li, RA:ronaldli@HKUCC.hku.hk | en_HK |
dc.identifier.authority | Li, RA=rp1352 | en_HK |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1023/A:1023624922787 | en_HK |
dc.identifier.pmid | 12766487 | - |
dc.identifier.scopus | eid_2-s2.0-0037898884 | en_HK |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-0037898884&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 8 | en_HK |
dc.identifier.issue | 3 | en_HK |
dc.identifier.spage | 269 | en_HK |
dc.identifier.epage | 275 | en_HK |
dc.identifier.isi | WOS:000182721900006 | - |
dc.identifier.issnl | 1360-8185 | - |