title: Cellular responses to chlorin-based photosensitizer DH-II-24 under darkness in human gastric adenocarcinoma AGS cells.
abstract: We investigated cellular responses to chlorin-based photosensitizer DH-II-24 under darkness in human gastric adenocarcinoma AGS cells. Cells were loaded with 0.5-10 μg/mL DH-II-24 for 12 h, and intracellular reactive oxygen species (ROS) and intracellular Ca(2+) levels, in situ tissue transglutaminase (tTGase) activity, cell viability, cell morphology and cell cycle were examined. DH-II-24 treatment had no effect on intracellular ROS production or cell morphology, and did not induce cell detachment at any concentrations tested. In addition, cell viability and cell cycle progression were not altered by the photosensitizer. However, DH-II-24 treatment elevated the basal level of intracellular Ca(2+) in a dose-dependent manner and inhibited tTGase activity without affecting tTGase expression levels. Furthermore, DH-II-24 inhibited lysophosphatidic acid-induced activation of tTGase in a dose-dependent manner. In contrast, photodynamic therapy (PDT) with 1 μg/mL DH-II-24 significantly elevated intracellular ROS and in situ tTGase activity in parallel with a rapid and large increase in intracellular Ca(2+) levels. DH-II-24-mediated PDT decreased cell viability and induced cell detachment. These results demonstrate that DH-II-24 treatment alone under darkness induced different cellular responses to DH-II-24-mediated PDT.
authors.affiliation: Department of Molecular and Cellular Biochemistry and Institute of Medical Scicence, Kangwon National University School of Medicine, Kangwon-do, Korea.
authors.forename: Young-Cheol
authors.initials: YC
authors.lastname: Lim
authors.forename: Je-Ok
authors.initials: JO
authors.lastname: Yoo
authors.forename: Seong-Sik
authors.initials: SS
authors.lastname: Kang
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.forename: Kwon-Soo
authors.initials: KS
authors.lastname: Ha
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D010778:Photochemotherapy; D011166:Porphyrins / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011503:Transglutaminases / Q000378:metabolism
chemical_list: C547071:DH-II-24 compound; D011166:Porphyrins; D017382:Reactive Oxygen Species; D011503:Transglutaminases; D002118:Calcium