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Differential cytotoxic responses to low‐ and high‐dose photodynamic therapy in human gastric and bladder cancer cells
Author(s) -
Yoo JeOk,
Lim YoungCheol,
Kim YoungMyeong,
Ha KwonSoo
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23231
Subject(s) - intracellular , propidium iodide , apoptosis , programmed cell death , trolox , cytotoxic t cell , cancer cell , chemistry , annexin , cancer research , bapta , microbiology and biotechnology , biology , medicine , biochemistry , cancer , oxidative stress , in vitro , antioxidant capacity
Here, we present differential cytotoxic responses to two different doses of photodynamic therapies (PDTs; low‐dose PDT [LDP] and high‐dose PDT [HDP]) using a chlorin‐based photosensitizer, DH‐II‐24, in human gastric and bladder cancer cells. Fluorescence‐activated cell sorting analysis using Annexin V and propidium iodide (PI) showed that LDP induced apoptotic cell death, whereas HDP predominantly caused necrotic cell death. The differential cytotoxic responses to the two PDTs were further confirmed by a DiOC 6 and PI double‐staining assay via confocal microscopy. LDP, but not HDP, activated caspase‐3, which was inhibited by Z‐VAD, Trolox, and BAPTA‐AM. LDP and HDP demonstrated opposite effects on intracellular reactive oxygen species (ROS)/Ca 2+ signals; LDP stimulated intracellular ROS production, contributing to a transient increase of intracellular Ca 2+ , whereas HDP induced a massive and prolonged elevation of intracellular Ca 2+ responsible for the transient production of intracellular ROS. In addition, the two PDTs also increased in situ transglutaminase 2 (TG2) activity, with a higher stimulation by HDP, and this increase in activity was prevented by Trolox, BAPTA‐AM, and TG2‐siRNA. LDP‐induced apoptotic cell death was strongly inhibited by Trolox and TG2‐siRNA and moderately suppressed by BAPTA‐AM. However, HDP‐mediated necrotic cell death was partially inhibited by BAPTA‐AM but not by TG2‐siRNA. Thus, these results demonstrate that LDP and HDP induced apoptotic and necrotic cell death by differential signaling mechanisms involving intracellular Ca 2+ , ROS, and TG2. J. Cell. Biochem. 112: 3061–3071, 2011. © 2011 Wiley‐Liss, Inc.