n-n-dimethylsphingenine has been researched along with Lung-Neoplasms* in 2 studies
2 other study(ies) available for n-n-dimethylsphingenine and Lung-Neoplasms
| Article | Year |
|---|---|
DMS triggers apoptosis associated with the inhibition of SPHK1/NF-κB activation and increase in intracellular Ca2+ concentration in human cancer cells.
N,N-Dimethyl-D-erythro-sphingosine (DMS) is known to induce cell apoptosis by specifically inhibiting sphingosine kinase 1 (SPHK1) and modulating the activity of cellular ceramide levels. The present study investigated the effects and the mechanism(s) of action of DMS in human lung cancer cells. We found that DMS dose-dependently suppressed cell proliferation and induced cell apoptosis in the human lung cancer cell line, A549. Mechanistically, treatment with DMS suppressed the activation of SPHK1 and nuclear factor-κB (NF-κB) p65, but increased intracellular [Ca2+]i in A549 cells. This study demonstrates that DMS triggers the apoptosis of human lung cancer cells through the modulation of SPHK1, NF-κB and calcium signaling. These molecules may represent targets for anticancer drug design. Topics: Adaptor Proteins, Signal Transducing; Apoptosis; Calcium; Caspase 3; Cell Line, Tumor; Cell Proliferation; DNA Fragmentation; Humans; Lung Neoplasms; NF-kappa B; Signal Transduction; Sphingosine | 2014 |
Enhancement of radiosensitivity by combined ceramide and dimethylsphingosine treatment in lung cancer cells.
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 G(1) 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. Topics: Animals; Apoptosis; bcl-2-Associated X Protein; bcl-X Protein; Carcinoma, Lewis Lung; Caspases; Cell Line, Tumor; Cell Survival; Gene Expression; Lung Neoplasms; Mice; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Radiation Tolerance; Radiation-Sensitizing Agents; Sphingosine | 2004 |