A novel photosensitizer DTPP-mediated photodynamic therapy induces oxidative stress and apoptosis through mitochondrial pathways in LA795 cells

Abstract

ObjectiveInvestigation of the effects of 5–5- (4-N, N-diacetoxylphenyl)-10,15,20- tetraphenylporphyrin (DTPP)-mediated photodynamic therapy (PDT) on oxidative stress and mitochondrial apoptosis in LA795 lung cancer cells. MethodsProteomics was used to identify differentially expressed proteins after PDT treatment. The apoptosis rate was determined by flow cytometry. Morphologic observation of apoptosis, reactive oxygen species (ROS) levels, antioxidant indices, nitric oxide (NO) content, mitochondrial membrane potential (MMP), and Caspase- 9 and Caspase-3 were determined by assays; apoptosis-related protein levels of Cytochrome (Cyto) c, Bcl- 2, Bax were determined by Western blot. ResultsTypical apoptosis morphology of LA795 cells was observed after PDT. The cells were mainly in the apoptosis death pathway with high cell apoptosis rates. The proteomics study observed the apoptosis-associated proteins, oxidative stress proteins, antioxidant proteins, the cytoskeletal protein and mitochondrial dysfunction in LA 795 cells. Additional results indicated that PDT could increase levels of ROS, NO; decrease glutathione (GSH) content and MMP; upregulated Bax, Cyto c, and Caspase-3 protein expression, inhibited Bcl-2 protein expression, and further induced cell apoptosis. The effect of DTPP-PDT on lung cancer was: first, mitochondrial Cyto c is released into the cytoplasm, then Caspase- 9 / Caspase-3 was activated, Bcl-2 decreased/Bax increased, initiating cell apoptosis. ConclusionDTPP-PDT could induce oxidative stress and apoptosis via mitochondrial pathways in LA795 cells.