Volatile Anesthetics Protect Cancer Cells against Tumor Necrosis Factor-related Apoptosis-inducing Ligand-induced Apoptosis via Caveolins
| Autor: | Anne N. Murphy, Brian P. Head, Atsushi Miyanohara, Yousuke T. Horikawa, Sameh S. Ali, Yoshitaka Kawaraguchi, David M. Roth, Hemal H. Patel, Fiona Murray, Piyush M. Patel |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Programmed cell death
Blotting Western Caveolin 1 Apoptosis Biology Transfection Article Natural killer cell Oxygen Consumption GTP-Binding Proteins Caveolae Cell Line Tumor Caveolin medicine Humans RNA Small Interfering Caspase 3 Reverse Transcriptase Polymerase Chain Reaction HCT116 Cells Cell biology Receptors TNF-Related Apoptosis-Inducing Ligand Anesthesiology and Pain Medicine medicine.anatomical_structure Anesthetic Cancer cell Anesthetics Inhalation Indicators and Reagents HT29 Cells medicine.drug Plasmids |
| Popis: | Background Volatile anesthetics have a dual effect on cell survival dependent on caveolin expression. The effect of volatile anesthetics on cancer cell survival and death after anesthetic exposure has not been well investigated. The authors examined the effects of isoflurane exposure on apoptosis and its regulation by caveolin-1 (Cav-1). Methods The authors exposed human colon cancer cell lines to isoflurane and proapoptotic stimuli and assessed what role Cav-1 plays in cell protection. They evaluated apoptosis using assays for nucleosomal fragmentation, cleaved caspase 3 expression, and caspase activity assays. To test the mechanism, they used pharmacologic inhibitors (i.e., pertussis toxin) and assessed changes in glycolysis. Results Apoptosis as measured by nucleosomal fragmentation was enhanced by isoflurane (1.2% in air) in HT29 (by 64% relative to control, P < 0.001) and decreased in HCT116 (by 23% relative to control, P < 0.001) cells. Knockdown of Cav-1 in HCT116 cells increased the sensitivity to apoptotic stimuli but not with scrambled small interfering RNA (siRNA) treatment (19.7 ± 0.4 vs. 20.0 ± 0.6, P = 0.7786 and 19.7 ± 0.5 vs. 16.3 ± 0.4, P = 0.0012, isoflurane vs. control in Cav-1 small interfering RNA vs. scrambled small interfering RNA treated cells, respectively). The protective effect of isoflurane with various exposure times on apoptosis was enhanced in HT29 cells overexpressing Cav-1 (P < 0.001 by two-way ANOVA). Pertussis toxin effectively blocked the antiapoptotic effect of isoflurane exhibited by Cav-1 in all cell lines. Cav-1 cells had increased glycolysis with isoflurane exposure; however, in the presence of tumor necrosis factor-related apoptosis-inducing ligand, this increase in glycolysis was maintained in HT29-Cav-1 but not control cells. Conclusion Brief isoflurane exposure leads to resistance against apoptosis via a Cav-1-dependent mechanism. |
| Databáze: | OpenAIRE |
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