title: The effects of dimethyl sulfoxide and retinoic acid on the cell growth and the phenotype of ovarian cancer cells.
abstract: We have compared the in vitro effects of the differentiation inducers dimethyl sulfoxide (DMSO) and retinoic acid (RA) on a polyclonal human ovarian cancer cell line (HOC-7). Density gradient fractionation of untreated cells reveals that a proportion of rapidly growing, polygonal cells with medium density is capable of spontaneous reversion into a slowly growing low-density phenotype with flattened morphology similar to non-transformed human ovarian surface epithelial cells. Clonal expansion of these low-density cells proves that the observed characteristics are stable for prolonged culture periods. Exposure of HOC-7 cells to DMSO and RA or removal of the serum from the medium is effective in enhancing the proportion of these low-density cells. Application of DMSO causes the cells to become flattened and elongated, and to develop rod-like protrusions. In these cytoplasmic extensions thick filament bundles are dominant. Immunofluorescence studies demonstrate that both untreated low-density subclones and DMSO-treated polyclonal cells are much more reactive for cytokeratin than medium-density subclones or untreated parental cells. Furthermore, immunocytochemistry and fixed-cell ELISA reveal 2- to 5-fold greater amounts of desmoplakins I and II and of fibronectin in low-density subclones and in DMSO-treated cells as compared to medium-density subclones and control cultures. RA exerts weaker effects on the phenotype of the cells. Both inducers reduce DNA synthesis and inhibit the anchorage-dependent and the anchorage-independent cell growth in a dose- and time-dependent manner. The restoration of the original morphology and growth rate after removal of the differentiation-inducing agents proves that the observed changes are reversible; this indicates that the cells do not become terminally differentiated.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Internal Medicine I, University of Vienna, Austria.
authors.forename: T W
authors.initials: TW
authors.lastname: Grunt
authors.forename: C
authors.initials: C
authors.lastname: Somay
authors.forename: M
authors.initials: M
authors.lastname: Pavelka
authors.forename: A
authors.initials: A
authors.lastname: Ellinger
authors.forename: E
authors.initials: E
authors.lastname: Dittrich
authors.forename: C
authors.initials: C
authors.lastname: Dittrich
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051180:Desmoplakins; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D005353:Fibronectins; D014212:Tretinoin; D004121:Dimethyl Sulfoxide