Apoptosis and autophagy induced by pyropheophorbide-α methyl ester-mediated photodynamic therapy in human osteosarcoma MG-63 cells.
Pyropheophorbide-α methyl ester (MPPa) was a second-generation photosensitizer with many potential applications. Here, we explored the impact of MPPa-mediated photodynamic therapy (MPPa-PDT) on the apoptosis and autophagy of human osteosarcoma (MG-63) cells as well as the relationships between apoptosis and autophagy of the cells, and investigated the related molecular mechanisms. We found that MPPa-PDT demonstrated the ability to inhibit MG-63 cell viability in an MPPa concentration- and light dose-dependent manner, and to induce apoptosis via the mitochondrial apoptosis pathway. Additionally, MPPa-PDT could also induce autophagy of MG-63 cell. Meanwhile, the ROS scavenger N-acetyl-L-cysteine (NAC) and the Jnk inhibitor SP600125 were found to inhibit the MPPa-PDT-induced autophagy, and NAC could also inhibit Jnk phosphorylation. Furthermore, pretreatment with the autophagy inhibitor 3-methyladenine or chloroquine showed the potential in reducing the apoptosis rate induced by MPPa-PDT in MG-63 cells. Our results indicated that the mitochondrial pathway was involved in MPPa-PDT-induced apoptosis of MG-63 cells. Meanwhile the ROS-Jnk signaling pathway was involved in MPPa-PDT-induced autophagy, which further promoted the apoptosis in MG-63 cells.
Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, No. 1 You Yi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, China.
Qiu
Q
Huang
Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, No. 1 You Yi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, China. ouyunsheng2001@163.com.
Yun-Sheng
YS
Ou
Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, No. 1 You Yi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, China.
Yong
Y
Tao
Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, No. 1 You Yi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, China.
Hang
H
Yin
Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, No. 1 You Yi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, China.
Ping-Hua
PH
Tu
D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; 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
Apoptosis; Autophagy; Osteosarcoma; Photodynamic therapy; Pyropheophorbide-α methyl ester