Hyperthermia induces apoptosis through endoplasmic reticulum and reactive oxygen species in human Osteosarcoma cells
Journal
International Journal of Molecular Sciences
Journal Volume
15
Journal Issue
10
Pages
17380-17395
Date Issued
2014
Author(s)
Abstract
Osteosarcoma (OS) is a relatively rare form of cancer, but OS is the most commonly diagnosed bone cancer in children and adolescents. Chemotherapy has side effects and induces drug resistance in OS. Since an effective adjuvant therapy was insufficient for treating OS, researching novel and adequate remedies is critical. Hyperthermia can induce cell death in various cancer cells, and thus, in this study, we investigated the anticancer method of hyperthermia in human OS (U-2 OS) cells. Treatment at 43 °C for 60 min induced apoptosis in human OS cell lines, but not in primary bone cells. Furthermore, hyperthermia was associated with increases of intracellular reactive oxygen species (ROS) and caspase-3 activation in U-2 OS cells. Mitochondrial dysfunction was followed by the release of cytochrome c from the mitochondria, and was accompanied by decreased anti-apoptotic Bcl-2 and Bcl-xL, and increased pro-apoptotic proteins Bak and Bax. Hyperthermia triggered endoplasmic reticulum (ER) stress, which was characterized by changes in cytosolic calcium levels, as well as increased calpain expression and activity. In addition, cells treated with calcium chelator (BAPTA-AM) blocked hyperthermia-induced cell apoptosis in U-2 OS cells. In conclusion, hyperthermia induced cell apoptosis substantially via the ROS, ER stress, mitochondria, and caspase pathways. Thus, hyperthermia may be a novel anticancer method for treating OS. ? 2014 by the authors; licensee MDPI, Basel, Switzerland.
SDGs
Other Subjects
beta actin; calcium; calpain 1; calpain 2; caspase 3; caspase 9; cytochrome c; glucose regulated protein 78; glucose regulated protein 94; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 2; protein Bak; protein Bax; protein bcl 2; protein bcl xl; reactive oxygen metabolite; reduced nicotinamide adenine dinucleotide phosphate oxidase; small interfering RNA; voltage dependent anion channel; 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; calpain; caspase 3; cytochrome c; egtazic acid; protein Bak; protein Bax; protein bcl 2; protein bcl x; reactive oxygen metabolite; apoptosis; apoptosis assay; Article; calcium transport; cell culture; chromatin condensation; controlled study; cytotoxicity; cytotoxicity assay; disorders of mitochondrial functions; endoplasmic reticulum stress; experimental hyperthermia; flow cytometry; human; human cell; mitochondrial membrane potential; osteosarcoma; osteosarcoma cell; protein expression; Western blotting; analogs and derivatives; antagonists and inhibitors; down regulation; drug effects; endoplasmic reticulum; endoplasmic reticulum stress; genetics; metabolism; mitochondrion; osteosarcoma; pathology; temperature; tumor cell line; upregulation; Apoptosis; bcl-2 Homologous Antagonist-Killer Protein; bcl-2-Associated X Protein; bcl-X Protein; Calpain; Caspase 3; Cell Line, Tumor; Cytochromes c; Down-Regulation; Egtazic Acid; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Humans; Mitochondria; Osteosarcoma; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; RNA, Small Interfering; Temperature; Up-Regulation
Publisher
MDPI AG
Type
journal article