1. Energy metabolism targeted drugs synergize with photodynamic therapy to potentiate breast cancer cell death.
- Author
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Feng X, Zhang Y, Wang P, Liu Q, and Wang X
- Subjects
- Acetylcysteine pharmacology, Antineoplastic Combined Chemotherapy Protocols, Apoptosis drug effects, Apoptosis physiology, Apoptosis radiation effects, Breast Neoplasms pathology, Breast Neoplasms physiopathology, Caspase 3 metabolism, Cell Line, Tumor, Cell Survival drug effects, Cell Survival physiology, Cell Survival radiation effects, Female, Free Radical Scavengers pharmacology, Human Umbilical Vein Endothelial Cells, Humans, MAP Kinase Kinase 4 metabolism, Mitochondrial Membranes drug effects, Mitochondrial Membranes physiology, Mitochondrial Membranes radiation effects, Photosensitizing Agents pharmacology, Reactive Oxygen Species metabolism, bcl-2-Associated X Protein metabolism, p38 Mitogen-Activated Protein Kinases metabolism, Antineoplastic Agents pharmacology, Breast Neoplasms therapy, Deoxyglucose pharmacology, Photochemotherapy methods, Pyruvates pharmacology
- Abstract
Malignant cells are highly dependent on aerobic glycolysis, which differs significantly from normal cells (the Warburg effect). Interference of this metabolic process has been considered as an innovative method for developing selective cancer therapy. A recent study demonstrated that the glycolysis inhibitor 2-deoxyglucose (2-DG) can potentiate PDT efficacy, whereas the possible mechanisms have not been carefully investigated. This study firstly proved the general potentiation of PDT efficacy by 2-DG and 3-bromopyruvate (3-BP) in human breast cancer MDA-MB-231 cells, and carefully elucidated the underlying mechanism in the process. Our results showed that both 2-DG and 3-BP could significantly promote a PDT-induced cell cytotoxic effect when compared with either monotherapy. Synergistic potentiation of mitochondria- and caspase-dependent cell apoptosis was observed, including a mitochondrial membrane potential (MMP) drop, Bax translocation, and caspase-3 activation. Besides, ROS generation and the expression of oxidative stress related proteins such as P38 MAPK phosphorylation and JNK phosphorylation were notably increased after the combined treatments. Moreover, when pretreated with the ROS scavenger N-acetylcysteine (NAC), the ROS generation, the MMP drop, cell apoptosis and cytotoxicity were differently inhibited, suggesting that ROS was vertical in the pro-apoptotic process induced by 2-DG/3-BP combined with PDT treatment. These results indicate that the combination of glycolytic antagonists and PDT may be a promising therapeutic strategy to effectively kill cancer cells.
- Published
- 2014
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