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Regulation of aberrant cell processes with non‐toxic doses of Sphingosine and Enigmol: initial investigation of the chemopreventive potential of natural and synthetic sphingoid bases in a cell model for progressive ovarian cancer
Author(s) -
Roberts Paul Christopher,
DoyonReale Nicole,
Baxa Andrea,
Schmelz Eva M
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a166-a
Subject(s) - sphingosine , sphingolipid , in vivo , ovarian cancer , biology , cell growth , cancer research , in vitro , cell culture , lipid signaling , pharmacology , cancer , microbiology and biotechnology , biochemistry , receptor , genetics
We have recently isolated mouse ovarian surface epithelium (MOSE) that spontaneously undergo transformation in vitro and characterized distinct transitional states. This model was used for the initial in vitro and in vivo evaluation of the chemopreventive and chemotherapeutic potential of sphingosine and the novel sphingosine analog Enigmol. A dose‐ and stage‐dependent growth inhibition and induction of cell death was seen with both compounds. A comparison to cells growing as multicellular spheroids indicated an association of these effects with the rate of proliferation. However, long‐term incubation with low concentrations of the sphingoid bases significantly increased the doubling time of the MOSE cells, which was not completely reversible after removal of the sphingolipids. This treatment also inhibited anchorage‐independent growth in soft agar of both intermediate and the most aggressive lines, indicating both chemopreventive and chemotherapeutic properties of these concentrations of sphingoid bases. Treatment with either sphingosine or Enigmol prevented or reversed the neoplastic progression of MOSE cells at distinct stages in vitro as measured by the expression of specific proteins associated with ovarian cancer progression. Thus, the use of low doses of sphingoid bases provides a promising strategy for both chemoprevention and chemotherapy of ovarian cancer. Supported by AICR grant 04B071 (to EMS), and a grant from the Elsa U. Pardee Foundation for Cancer Research (to PCR)