Hematoporphyrin monomethyl ether photodynamic damage on HeLa cells by means of reactive oxygen species production and cytosolic free calcium concentration elevation.
Hematoporphyrin monomethyl ether (HMME) is a novel and promising porphyrin-related photosensitizer for photodynamic therapy (PDT). HMME-PDT-induced cell death and its mechanisms were investigated in HeLa cells. We demonstrated that HMME-PDT could induce cell death through both necrosis and apoptosis. Sodium azide (the singlet oxygen quencher) or D-mannitol (the hydroxyl radical scavenger) could protect HeLa cells from the apoptosis and necrosis induced by HMME-PDT, showing that reactive oxygen species (ROS), such as singlet oxygen and hydroxyl radical, played a decisive role in HMME-PDT-induced HeLa cells death. Sodium azide or D-mannitol also inhibited HMME-PDT-mediated [Ca2+]i elevation. Cytochrome C (Cyto C) release from mitochondria into cytosol and Caspase-3 activation after HMME-PDT were inhibited by BAPTA/AM (an intracellular calcium chelator). These results demonstrated that ROS generated in HeLa cells by HMME-PDT-induced apoptosis may be through [Ca2+]i elevation which mediates Cyto C release and Caspase-3 activition and initiates the subsequent late stages of apoptosis.
Ding
Xinmin
X
Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, China.
Xu
Qinzhi
Q
Liu
Fanguang
F
Zhou
Pingkun
P
Gu
Ying
Y
Zeng
Jing
J
An
Jing
J
Dai
Weide
W
Li
Xiaosong
X
D017209:Apoptosis; D002118:Calcium / Q000378:metabolism / Q000493:pharmacokinetics; D016923:Cell Death; D005260:Female; D006367:HeLa Cells; D006415:Hematoporphyrins / Q000494:pharmacology*; D006801:Humans; D009336:Necrosis; D010778:Photochemotherapy; D017382:Reactive Oxygen Species
D006415:Hematoporphyrins; D017382:Reactive Oxygen Species; C494379:hematoporphyrin monomethyl ether; D002118:Calcium