Enhancement of radiosensitivity by combined ceramide and dimethylsphingosine treatment in lung cancer cells
Experimental & Molecular Medicine
; : 411-419, 2004.
Article
in En
| WPRIM
| ID: wpr-76973
Responsible library:
WPRO
ABSTRACT
Ceramide generated from sphingomyelin in response to ionizing radiation has been implicated as a second messenger to induce cellular proapoptotic signals. Both ceramide and its metabolic inhibitor, N, N-dimethyl-D-erythro-sphingosine (DMS), might lead to sustained ceramide accumulation in cells more efficiently, thereby sensitizing them to gamma-radiation-induced cell death. To delineate this problem, the clonogenic survival of Lewis lung carcinoma (LLC) cells was evaluated following exposure to radiation together with or without C2-ceramide, DMS, or both. The treatment of ceramide/DMS synergistically decreased the survival of the irradiated cells compared with treatment with ceramide or DMS alone. Ceramide/DMS-treated cells displayed several apoptotic features after gamma-irradiation, including increased sub G1 population, TUNEL-positive fraction, and poly-(ADP-ribose) polymerase (PARP) cleavage. We also observed ceramide/ DMS induced disruption of mitochondrial membrane potential (MMP) and activation of caspase- 9 and -3 in a radiation-dose-dependent manner. Furthermore, pretreatment of LLC cells with ceramide/DMS not only increased the protein expression level of Bax, but also decreased Bcl-2 after gamma-irradiation. Taken together, the present study indicates that the radiosensitizing activity of ceramide/DMS on LLC cells most likely reflects the dominance of pro-apoptotic signals related to the mitochondria-dependent pathway.
Key words
Full text:
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Index:
WPRIM
Main subject:
Radiation-Sensitizing Agents
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Radiation Tolerance
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Sphingosine
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Gene Expression
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Cell Survival
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Proto-Oncogene Proteins
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Apoptosis
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Carcinoma, Lewis Lung
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Proto-Oncogene Proteins c-bcl-2
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Caspases
Limits:
Animals
Language:
En
Journal:
Experimental & Molecular Medicine
Year:
2004
Type:
Article