Role of nuclear factor-kappa B in colon cancer cell apoptosis mediated by aminopyropheophorbide photosensitization.
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)-kappa B 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-kappa B turned out to be involved in an antiapoptotic response to APP-mediated photosensitization because the HCT-116 cell line expressing the dominant negative mutant of inhibitor-kappa B alpha 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.
Matroule
J Y
JY
Laboratory of Virology, University of Liège, Belgium.
Hellin
A C
AC
Morlière
P
P
Fabiano
A S
AS
Santus
R
R
Merville
M P
MP
Piette
J
J
D017209:Apoptosis; D001483:Base Sequence; D002734:Chlorophyll / Q000031:analogs & derivatives / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015342:DNA Probes / Q000235:genetics; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D015342:DNA Probes; D016328:NF-kappa B; D017319:Photosensitizing Agents; D002734:Chlorophyll