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Role of Nuclear Factor‐KB in Colon Cancer Cell Apoptosis Mediated by Aminopyropheophorbide Photosensitization
Author(s) -
Matroule JeanYves,
Hellin AnneCecile,
Morliere Patrice,
Fabiano A.S.,
Santus Rend,
Merville MariePaule,
Piette Jacques
Publication year - 1999
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1999.tb08249.x
Subject(s) - photosensitizer , apoptosis , fragmentation (computing) , dna fragmentation , chromatin , photodynamic therapy , microbiology and biotechnology , dapi , dna laddering , chemistry , dna damage , cancer cell , cytotoxic t cell , programmed cell death , biology , dna , in vitro , biochemistry , cancer , genetics , photochemistry , ecology , organic chemistry
Aminopyropheophorbide (APP) is a second generation of photosensitizer for photodynamic therapy (PDT). We demonstrated that APP strongly absorbed red light and, after being taken up by colon cancer cells (HCT‐116 cells), was localized in cytoplasmic and internal membranes but not in mitochondria. The APP‐mediated photosensitization was cytotoxic for HCT‐116 cells through an induction of apoptosis. Indeed, DNA fragmentation (DNA laddering and terminal deoxyuridine nick‐end labeling) and chromatin condensation (4′,6‐diamidine‐2′‐phenylindole staining) could be visualized soon after photosensitization. Because nuclear factor (NF)‐KB is involved in the response to many photosensitizers, we also demonstrated its nuclear translocation in two waves: a rapid and transient one, followed by a slow and sustained phase. The NF‐KB turned out to be involved in an antia‐poptotic response to APP‐mediated photosensitization because the HCT‐116 cell line expressing the dominant negative mutant of inhibitor‐KBα was more sensitive to apoptosis as measured by DNA fragmentation and caspase activation. These data unambiguously show that a membrane‐located photosensitizer can lead to effective apoptosis, reinforcing the idea that PDT can be an effective means to eradicate colon cancer cells.