Nuclear Lipid Microdomain as Resting Place of Dexamethasone to Impair Cell Proliferation

International Journal of Molecular Sciences

Samuela Cataldi²  Michela Codini⁴  Giacomo Cascianelli²  Sabina Tringali³  Anna Rita Tringali³  Andrea Lazzarini²  Alessandro Floridi²  Elisa Bartoccini²  Mercedes Garcia-Gil¹  Remo Lazzarini²  Francesco Saverio Ambesi-Impiombato⁵  Francesco Curcio⁵  Tommaso Beccari⁴  Elisabetta Albi² 

[1] Department of Biology, University of Pisa, 56127 Pisa, Italy; E-Mail:;Laboratory of Nuclear Lipid BioPathology, Crabion, 06074 Perugia, Italy; E-Mails:;Laboratory of Clinical Pathology, 96011 Augusta-Siracusa, Italy; E-Mails:;Department of Pharmaceutical Science, University of Perugia, 06100 Perugia, Italy; E-Mails:;Department of Clinical and Biological Sciences, University of Udine, 33100 Udine, Italy; E-Mails:

关键词: dexametasone;    lymphoma;    nuclear lipid microdomains;    sphingomyelin;    sphingomyelinase;    sphingomyelin-synthase;   

DOI  :  10.3390/ijms151119832

来源: mdpi

【 摘 要 】

The action of dexamethasone is initiated by, and strictly dependent upon, the interaction of the drug with its receptor followed by its translocation into the nucleus where modulates gene expression. Where the drug localizes at the intranuclear level is not yet known. We aimed to study the localization of the drug in nuclear lipid microdomains rich in sphingomyelin content that anchor active chromatin and act as platform for transcription modulation. The study was performed in non-Hodgkin’s T cell human lymphoblastic lymphoma (SUP-T1 cell line). We found that when dexamethasone enters into the nucleus it localizes in nuclear lipid microdomains where influences sphingomyelin metabolism. This is followed after 24 h by a cell cycle block accompanied by the up-regulation of cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin-dependent kinase inhibitor 1B (CDKN1B), growth arrest and DNA-damage 45A (GADD45A), and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) genes and by the reduction of signal transducer and activator of transcription 3 (STAT3) and phospho signal transducer and activator of transcription 3 (phoshoSTAT3) proteins. After 48 h some cells show morphological changes characteristic of apoptosis while the number of the cells that undergo cell division and express B-cell lymphoma-2 (Bcl-2) is very low. We suggest that the integrity of nuclear lipid microdomains is important for the response to glucocorticoids of cancer cells.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.