Induction of cell death by pyropheophorbide-α methyl ester-mediated photodynamic therapy in lung cancer A549 cells.
Pyropheophorbide-α methyl ester (MPPa) was a promising photosensitizer with stable chemical structure, strong absorption, higher tissue selectivity and longer activation wavelengths. The present study investigated the effect of MPPa-mediated photodynamic treatment on lung cancer A549 cells as well as the underlying mechanisms. Cell Counting Kit-8 was employed for cell viability assessment. Reactive oxygen species levels were determined by fluorescence microscopy and flow cytometry. Cell morphology was evaluated by Hoechst staining and transmission electron microscopy. Mitochondrial membrane potential, cellular apoptosis and cell cycle distribution were evaluated flow-cytometrically. The protein levels of apoptotic effectors were examined by Western blot. We found that the photocytotoxicity of MPPa showed both drug- and light- dose dependent characteristics in A549 cells. Additionally, MPPa-PDT caused cell apoptosis by reducing mitochondrial membrane potential, increasing reactive oxygen species (ROS) production, inducing caspase-9/caspase-3 signaling activation as well as cell cycle arrest at G0/G1phase. These results suggested that MPPa-PDT mainly kills cells by apoptotic mechanisms, with overt curative effects, indicating that MPPa should be considered a potent photosensitizer for lung carcinoma treatment.
Department of respiratory medicine, The Central Hospital of Xiaogan, Xiaogan, China.
Ping-Hua
PH
Tu
Department of respiratory medicine, The Central Hospital of Xiaogan, Xiaogan, China.
Wen-Jun
WJ
Huang
Department of respiratory medicine, The Central Hospital of Xiaogan, Xiaogan, China.
Zhan-Ling
ZL
Wu
Department of respiratory medicine, The Central Hospital of Xiaogan, Xiaogan, China.
Qing-Zhen
QZ
Peng
Department of respiratory medicine, The Central Hospital of Xiaogan, Xiaogan, China.
Zhi-Bin
ZB
Xie
Department of respiratory medicine, The Central Hospital of Xiaogan, Xiaogan, China.
Ji
J
Bao
Department of respiratory medicine, The Central Hospital of Xiaogan, Xiaogan, China.
Ming-Hua
0000-0002-9603-2925
MH
Zhong
D000072283:A549 Cells; D053148:Caspase 3 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D017319:Photosensitizing Agents; D011166:Porphyrins; D017382:Reactive Oxygen Species; C452939:pyropheophorbide-a methylester; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9
A549 cells; apoptosis; cell cycle; photodynamic therapy; pyropheophorbide-α methyl ester; reactive oxygen species