Sphingolipid Metabolites Modulate Dielectric Characteristics of Cells in a Mouse Ovarian Cancer Progression Model

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dc.contributorSchool of Biomedical Engineering and Sciences. Bioelectromechanical Systems Laboratoryen
dc.contributorEngineering Science and Mechanics Departmenten
dc.contributorBiomedical Sciences and Pathobiologyen
dc.contributorHuman Nutrition, Foods, and Exerciseen
dc.contributor.authorSalmanzadeh, Alirezaen
dc.contributor.authorElvington, Elizabeth S.en
dc.contributor.authorRoberts, Paul C.en
dc.contributor.authorSchmelz, Eva M.en
dc.contributor.authorDavalos, Rafael V.en
dc.contributor.departmentSchool of Biomedical Engineering and Sciencesen
dc.date.accessed2015-04-17en
dc.date.accessioned2015-04-20T22:22:11Zen
dc.date.available2015-04-20T22:22:11Zen
dc.date.issued2013-03-27en
dc.description.abstractCurrently, conventional cancer treatment regimens often rely upon highly toxic chemotherapeutics or target oncogenes that are variably expressed within the heterogeneous cell population of tumors. These challenges highlight the need for novel treatment strategies that (1) are non-toxic yet able to at least partially reverse the aggressive phenotype of the disease to a benign or very slow-growing state, and (2) act on the cells independently of variably expressed biomarkers. Using a label-independent rapid microfluidic cell manipulation strategy known as contactless dielectrophoresis (cDEP), we investigated the effect of non-toxic concentrations of two bioactive sphingolipidmetabolites, sphingosine (So), with potential anti-tumor properties, and sphingosine-1-phosphate (S1P), a tumor-promoting metabolite, on the intrinsic electrical properties of early and late stages of mouse ovarian surface epithelial (MOSE) cancer cells. Previously, we demonstrated that electrical properties change as cells progress from a benign early stage to late malignant stages. Here, we demonstrate an association between So treatment and a shift in the bioelectrical characteristics of late stage MOSE (MOSE-L) cells towards a profile similar to that of benign MOSE-E cells. Particularly, the specific membrane capacitance of MOSE-L cells shifted toward that of MOSE-E cells, decreasing from 23.94 ± 2.75 to 16.46 ± 0.62 mF m_2 after So treatment, associated with a decrease in membrane protrusions. In contrast, S1P did not reverse the electrical properties of MOSE-L cells. This work is the first to indicate that treatment with non-toxic doses of So correlates with changes in the electrical properties and surface roughness of cells. It also demonstrates the potential of cDEP to be used as a new, rapid technique for drug efficacy studies, and for eventually designing more personalized treatment regimens.en
dc.description.sponsorshipNational Institutes of Health - 1R21 CA173092-01en
dc.description.sponsorshipNational Institutes of Health -RO1 CA118846en
dc.description.sponsorshipNational Science Foundation (U.S.) - Grant no. EFRI 0938047en
dc.description.sponsorshipVirginia Tech. Institute for Critical Technology and Applied Scienceen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationSalmanzadeh, A., Elvington, E. S., Roberts, P. C., Schmelz, E. M., & Davalos, R. V. (2013). Sphingolipid metabolites modulate dielectric characteristics of cells in a mouse ovarian cancer progression model. Integrative Biology, 5(6), 843-852. doi: 10.1039/C3IB00008Gen
dc.identifier.doihttps://doi.org/10.1039/C3IB00008Gen
dc.identifier.issn1757-9694en
dc.identifier.urihttp://hdl.handle.net/10919/51722en
dc.identifier.urlhttp://pubs.rsc.org/en/content/articlelanding/2013/ib/c3ib00008gen
dc.language.isoenen
dc.publisherThe Royal Society of Chemistryen
dc.relation.ispartofseriesOpen access articles from Integrative Biologyen
dc.relation.urihttp://pubs.rsc.org/en/journals/articlecollectionlanding?sercode=ib&themeid=ab0f94be-eff2-4286-b96e-367458372850en
dc.rightsCreative Commons Attribution-NonCommercial 3.0 Unporteden
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/en
dc.subjectCancer treatmenten
dc.subjectContactless dielectrophoresis (cDEP)en
dc.subjectAnti-cancer agentsen
dc.subjectMouse ovarian canceren
dc.titleSphingolipid Metabolites Modulate Dielectric Characteristics of Cells in a Mouse Ovarian Cancer Progression Modelen
dc.title.serialIntegrative Biologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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