PMID- 18414010 OWN - NLM STAT- MEDLINE DCOM- 20080804 LR - 20240308 IS - 1016-8478 (Print) IS - 1016-8478 (Linking) VI - 25 IP - 2 DP - 2008 Apr 30 TI - N-acetylphytosphingosine enhances the radiosensitivity of lung cancer cell line NCI-H460. PG - 224-30 AB - Ceramides are well-known second messengers that induce apoptosis in various kinds of cancer cells, and their effects are closely related to radiation sensitivity. Phytoceramides, the yeast counterparts of the mammalian ceramides, are also reported to induce apoptosis. We investigated the effect of a novel ceramide derivative, N-acetylphytosphingosine (NAPS), on the radiosensitivity of NCI-H460 human lung carcinoma cells and its differential cytotoxicity in tumor and normal cells. The combination of NAPS with radiation significantly increased clonogenic cell death and caspase-dependent apoptosis. The combined treatment greatly increased Bax expression and Bid cleavage, but not Bcl-2 expression. However, there was no effect on radiosensitivity and apoptosis in BEAS2B cells, which derive from normal human bronchial epithelium. Cell proliferation and DNA synthesis were significantly inhibited by NAPS in both NCI-H460 and BEAS2B cells, but only the BEAS2B cells recovered by 48h after removal of the NAPS. Furthermore, the NCI-H460 cells underwent more DNA fragmentation than the BEAS2B cells in response to NAPS. Our results indicate that NAPS may be a potential radiosensitizing agent with differential effects on tumor vs. normal cells. FAU - Han, Youngsoo AU - Han Y AD - Laboratory of Radiation Sensitization and Protection, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Korea. FAU - Kim, Kisung AU - Kim K FAU - Shim, Ji-Young AU - Shim JY FAU - Park, Changsoe AU - Park C FAU - Song, Jie-Young AU - Song JY FAU - Yun, Yeon-Sook AU - Yun YS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080331 PL - United States TA - Mol Cells JT - Molecules and cells JID - 9610936 RN - 0 (Cytostatic Agents) RN - 0 (Sphingolipids) RN - 0 (bcl-2-Associated X Protein) RN - EC 3.4.22.- (Caspases) RN - RZ4494XR10 (N-acetylphytosphingosine) SB - IM EIN - Mol Cells. 2009 Jan;27(1):125 MH - Caspases/metabolism MH - Cell Death/drug effects/radiation effects MH - Cell Line, Tumor MH - Cell Survival/drug effects/radiation effects MH - Clone Cells MH - Cytostatic Agents/pharmacology MH - Enzyme Activation/drug effects/radiation effects MH - Gamma Rays MH - Humans MH - Lung Neoplasms/enzymology/*pathology MH - Radiation Tolerance/*drug effects MH - Sphingolipids/*pharmacology MH - bcl-2-Associated X Protein/metabolism EDAT- 2008/04/17 09:00 MHDA- 2008/08/05 09:00 CRDT- 2008/04/17 09:00 PHST- 2008/04/17 09:00 [pubmed] PHST- 2008/08/05 09:00 [medline] PHST- 2008/04/17 09:00 [entrez] AID - S1016-8478(23)17574-1 [pii] PST - ppublish SO - Mol Cells. 2008 Apr 30;25(2):224-30. Epub 2008 Mar 31.