title: Sphingolipid metabolites modulate dielectric characteristics of cells in a mouse ovarian cancer progression model.
abstract: Currently, 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 sphingolipid metabolites, 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.
authors.affiliation: Bioelectromechanical Systems Laboratory, School of Biomedical Engineering and Sciences, Virginia Tech-Wake Forest University, Blacksburg, VA 24061, USA.
authors.forename: Alireza
authors.initials: A
authors.lastname: Salmanzadeh
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Elvington
authors.forename: Paul C
authors.initials: PC
authors.lastname: Roberts
authors.forename: Eva M
authors.initials: EM
authors.lastname: Schmelz
authors.forename: Rafael V
authors.initials: RV
authors.lastname: Davalos
mesh_terms: D000818:Animals; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D018450:Disease Progression; D004586:Electrophoresis; D005260:Female; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D044085:Microfluidics; D008954:Models, Biological; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism*
chemical_list: D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine