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9-Hydroxypheophorbide alpha-induced apoptotic death of MCF-7 breast cancer cells is mediated by c-Jun N-terminal kinase activation.

Authors
Choi, SE; Sohn, S; Cho, JW; Shin, EA; Song, PS; Kang, Y
Citation
Journal of photochemistry and photobiology. B, Biology, 73(1-2):101-107, 2004
Journal Title
Journal of photochemistry and photobiology. B, Biology
ISSN
1011-13441873-2682
Abstract
Recently, we synthesized 9-hydroxypheophorbide alpha (9-HPbD), a new chlorophyll-derived photosensitizer. The photo-treatment of MCF-7 human breast cancer cells with 20 kJ/m2 of red light after 5 microM 9-HPbD pretreatment induced cell death, showed typical apoptotic features, i.e., chromatin condensation, phosphatidyl serine externalization, membrane blebbing, and apoptotic bodies with an intact plasma membrane structure. To elucidate the mechanism of 9-HPbD-induced apoptosis, various mediators of the apoptosis were investigated. Release of cytochrome c from mitochondria into the cytosol was distinct 9 h after irradiation, while the levels of most apoptosis-related molecules such as Fas, FasL, Bcl-2, Bax and p53 were unchanged. Furthermore, caspase-9 activated by released cytochrome c was not significantly activated after 9-HPbD-photosensitization. On the other hand, stress-activated protein kinases such as p38 and c-Jun N-terminal kinase (JNK) were activated 1 h after irradiation. Blocking of JNK signaling by transfecting with the dominant negative from of the JNK gene significantly reduced 9-HPbD-induced cell death. Our data show that photosensitization with the new photosensitizer 9-HPbD could induce the apoptotic death of MCF-7 breast cancer cell and that this death is mediated by stress-activated signal through JNK.
MeSH terms
Apoptosis/*drug effectsBlotting, WesternCell Line, TumorChlorophyll/analogs & derivatives/*pharmacologyEnzyme ActivationHumansJNK Mitogen-Activated Protein KinasesMicroscopy, ElectronMitogen-Activated Protein Kinases/*metabolism
PMID
14732256
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
손, 성향강, 엽
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