title: Mitochondrial pathway and endoplasmic reticulum stress participate in the photosensitizing effectiveness of AE-PDT in MG63 cells.
abstract: Photodynamic therapy (PDT) is a promising treatment in cancer therapy, with a photosensitizer activated by visible light. Aloe-emodin (AE) is a promising photosensitive agent. In this study, the photosensitizing effects and possible mechanisms of AE-PDT in MG63 cells were evaluated. The efficiency of AE-PDT was analyzed by MTT assay. The mode of cell death was investigated by Hoechst 33,342 staining and flow cytometer. The intracellular distribution of AE was detected with confocal microscopy. The formation of reactive oxygen species (ROS) was detected by DCFH-DA. The mitochondrial membrane potential (MMP) was measured by Rhodamine 123. The expression of proteins including cytochrome c, caspase-3, -9, and -12, CHOP and GRP78 was detected by western blot. Apoptosis is the primary mode of cell death in our study, which occurs in a manner of depending on AE concentration and irradiation dose. Confocal microscopy showed that AE was primarily localized on the mitochondria and endoplasmic reticulum (ER) of MG63 cells. AE-PDT resulted in rapid increases of intracellular ROS production, which reached a peak at 2 h, followed by declining of mitochondrial membrane potential, releasing of cytochrome c from mitochondria into the cytoplasm, and up-regulation of caspase-3, -9, and -12, CHOP and GRP78. These results suggest that death of MG63 cells induced by AE-PDT is triggered by ROS. Meanwhile, Mitochondria and ER serve as the subcellular targets, which are responsible for AE-PDT-induced death of MG63 cells.
authors.affiliation: Department of Rehabilitation, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Kai-Ting
authors.initials: KT
authors.lastname: Li
authors.affiliation: Department of Rehabilitation, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Rehabilitation, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Da-Wu
authors.initials: DW
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Chinese Medicine Hospital of Longquan, Chengdu, China.
authors.forename: Qin-Qin
authors.initials: QQ
authors.lastname: Duan
authors.affiliation: Department of Rehabilitation, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Si
authors.initials: S
authors.lastname: Tian
authors.affiliation: Department of Rehabilitation, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Juan-Wen
authors.initials: JW
authors.lastname: He
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Yun-Sheng
authors.initials: YS
authors.lastname: Ou
authors.affiliation: Department of Rehabilitation, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Ding-Qun
authors.initials: DQ
authors.lastname: Bai
mesh_terms: D000880:Anthraquinones / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000880:Anthraquinones; D015415:Biomarkers; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D024101:Mitochondrial Proteins; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; C518327:aloe emodin
keywords: Aloe emodin; endoplasmic reticulum; mitochondrial; osteosarcoma; photodynamic therapy