TY - JOUR
T1 - Isofraxidin, a potent reactive oxygen species (ROS) scavenger, protects human leukemia cells from radiation-induced apoptosis via ROS/mitochondria pathway in p53-independent manner
AU - Li, Peng
AU - Zhao, Qing Li
AU - Wu, Li Hua
AU - Jawaid, Paras
AU - Jiao, Yu Fei
AU - Kadowaki, Makoto
AU - Kondo, Takashi
N1 - Funding Information:
Acknowledgments This research was supported in part by a Grant-in-Aid for the Cooperative Research Project from Joint Usage/ Research Center (Joint Usage/Research Center for Science-Based Natural Medicine) Institute of Natural Medicine. University of Toy-ama in 2013; in part by the International Exchange Fund of the Sugitani campus (Medical and Pharmacy) (A) in 2012, University of Toyama, Japan.
PY - 2014/6
Y1 - 2014/6
N2 - Ionizing radiation (IR) leads to oxidizing events such as excessive reactive oxygen species (ROS) in the exposed cells, resulting in further oxidative damage to lipids, proteins and DNA. To screen the potential radioprotective drug, the intracellular ROS was measured in irradiated U937 cells pretreated with 80 candidate traditional herbal medicine, respectively. Isofraxidin (IF) was one possible radio-protector in these 80 drugs. This study investigated the radio-protective role of IF, a Coumarin compound, in human leukemia cell lines, for the first time. Results indicate that IF protects against IR-induced apoptosis in U937 cells in the time- and concentration- dependent manner. IF decreases IR-induced intracellular ROS generation, especially hydroxyl radicals formation, inhibits IR-induced mitochondrial membrane potential loss and reduces IR-induced high intracellular Ca 2+ levels regardless of ER stress. IF down-regulates the expression of caspase-3, phospho-JNK, phospho-p38 and activates Bax in mitochondria. IF inhibits cytochrome c release from mitochondria to cytosol. IF also moderates IR-induced Fas externalization and caspase-8 activation. IF also exhibits significant protection against IR-induced cell death in other leukemia cell lines such as Molt-4 cells and HL60 cells regardless of p53. Taken together, the data demonstrate that IF protects leukemia cells from radiation-induced apoptosis via ROS/mitochondria pathway in a p53-independent manner.
AB - Ionizing radiation (IR) leads to oxidizing events such as excessive reactive oxygen species (ROS) in the exposed cells, resulting in further oxidative damage to lipids, proteins and DNA. To screen the potential radioprotective drug, the intracellular ROS was measured in irradiated U937 cells pretreated with 80 candidate traditional herbal medicine, respectively. Isofraxidin (IF) was one possible radio-protector in these 80 drugs. This study investigated the radio-protective role of IF, a Coumarin compound, in human leukemia cell lines, for the first time. Results indicate that IF protects against IR-induced apoptosis in U937 cells in the time- and concentration- dependent manner. IF decreases IR-induced intracellular ROS generation, especially hydroxyl radicals formation, inhibits IR-induced mitochondrial membrane potential loss and reduces IR-induced high intracellular Ca 2+ levels regardless of ER stress. IF down-regulates the expression of caspase-3, phospho-JNK, phospho-p38 and activates Bax in mitochondria. IF inhibits cytochrome c release from mitochondria to cytosol. IF also moderates IR-induced Fas externalization and caspase-8 activation. IF also exhibits significant protection against IR-induced cell death in other leukemia cell lines such as Molt-4 cells and HL60 cells regardless of p53. Taken together, the data demonstrate that IF protects leukemia cells from radiation-induced apoptosis via ROS/mitochondria pathway in a p53-independent manner.
KW - Apoptosis
KW - Calcium
KW - Isofraxidin
KW - Mitochondria
KW - Radio-protection
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=84902378022&partnerID=8YFLogxK
U2 - 10.1007/s10495-014-0984-1
DO - 10.1007/s10495-014-0984-1
M3 - 学術論文
C2 - 24692054
AN - SCOPUS:84902378022
SN - 1360-8185
VL - 19
SP - 1043
EP - 1053
JO - Apoptosis
JF - Apoptosis
IS - 6
ER -