Role of Nuclear Factor-κB in Colon Cancer Cell Apoptosis Mediated by Aminopyropheophorbide Photosensitization

Abstract

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.

NF‐κB in Photodynamic Therapy: Discrepancies of a Master Regulator

“…A HCT116 mutant cell line stably expressing a dominant negative version of IkBαS32, S36A does not respond to PPME‐PDT and APP‐PDT in term of NF‐κB activation (29,30). Survival rate of the IκBαS32, S36A‐expressing cells was decreased versus wild type cells.…”

Uses of Photodynamic Therapy in Premalignant and Malignant Lesions of the Gastrointestinal Tract Beyond the Esophagus

“…Matroule et al at the University of Toulouse, France, studied the use of pyropheophorbide, a methylester PDT, in a colon cancer cell line. 133 This drug is known to be a membrane-located photosensitizer that can recruit interleukin receptors to trigger nuclear factor kappa B transcription factor activation inducing apoptosis (programmed cell death) as measured by DNA fragmentation and caspase activity. 134 Because this photosensitizer is cationic, this report would seem to confirm the findings of other investigators that the overall ionic charge of a photosensitizer or photoimmuneo-conjugate is important to effective drug delivery and subsequent photoactivation.…”

Photodynamic therapy in colorectal cancer treatment—The state of the art in preclinical research

“…This mechanism is separated from the one leading to NF-κB which was shown to be activated by the enrollment of the IL-1 transduction pathway [53]. Another photosensitizer of this class, aminopyropheophorbide, localized predominantly in lysosomes (not in mitochondria) of CRC HT-116 cells, under irradiation with red light induced apoptosis in which NF-κB was involved, similarly as described above, in a rapid and transient wave [54].…”