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Growth inhibitory effects of sodium phenylacetate (NSC 3039) on ovarian carcinoma cells in vitro.

Publication ,  Journal Article
Ferrandina, G; Melichar, B; Loercher, A; Verschraegen, CF; Kudelka, AP; Edwards, CL; Scambia, G; Kavanagh, JJ; Abbruzzese, JL; Freedman, RS
Published in: Cancer Res
October 1, 1997

The aim of this study was to determine the antiproliferative activity of sodium phenylacetate (NaPa) against ovarian carcinoma cell lines. NaPa induced a dose-dependent inhibition (IC50 from 12 mM to >20 mM) of all ovarian carcinoma cell lines, although the sensitivity of individual lines to NaPa varied. Both cisplatin-sensitive and -resistant cell lines responded to NaPa, and growth-inhibitory activity was also detected against cells freshly isolated from malignant ascites of previously treated patients. The growth inhibitory effects that were produced by NaPa were time dependent, showing a maximum effect at 72 h, and were not associated with cytotoxic action. Growth inhibitory effects of NaPa were also reversible. After 48- and 72-h exposures to NaPa, a reduction in the percentage of cells in the S-phase was detected, with a concomitant recruitment of cells in the G0-G1 phase. Treatment with NaPa after different exposure times did not significantly increase the proportion of cells undergoing apoptosis. NaPa also produced a significant reduction in the percentage of cyclin-D1- and p21/ras-positive cells and in the percentage of cells positive for bcl-2, whereas the percentages of bax/p21-positive cells increased. NaPa produced minimal, if any, alterations of expression of HLA class I and transforming growth factor beta1 antigens. In contrast, the percentage of transforming growth factor beta2-positive cells decreased after exposure to NaPa. The combination of NaPa with cisplatin resulted in an additive inhibitory effect. Our results show, for the first time, that NaPa inhibits the growth of ovarian carcinoma cell lines and the cells from malignant ascites of chemotherapy-treated patients with ovarian carcinoma. The growth-inhibitory properties of NaPa suggest that this molecule could represent a prototype of a new class of compounds with possible therapeutic potential in patients with ovarian carcinoma.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

October 1, 1997

Volume

57

Issue

19

Start / End Page

4309 / 4315

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Phenylacetates
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Humans
  • Growth Inhibitors
  • Female
  • Dose-Response Relationship, Drug
  • Cystadenocarcinoma, Serous
  • Cisplatin
 

Citation

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MLA
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Ferrandina, G., Melichar, B., Loercher, A., Verschraegen, C. F., Kudelka, A. P., Edwards, C. L., … Freedman, R. S. (1997). Growth inhibitory effects of sodium phenylacetate (NSC 3039) on ovarian carcinoma cells in vitro. Cancer Res, 57(19), 4309–4315.
Ferrandina, G., B. Melichar, A. Loercher, C. F. Verschraegen, A. P. Kudelka, C. L. Edwards, G. Scambia, J. J. Kavanagh, J. L. Abbruzzese, and R. S. Freedman. “Growth inhibitory effects of sodium phenylacetate (NSC 3039) on ovarian carcinoma cells in vitro.Cancer Res 57, no. 19 (October 1, 1997): 4309–15.
Ferrandina G, Melichar B, Loercher A, Verschraegen CF, Kudelka AP, Edwards CL, et al. Growth inhibitory effects of sodium phenylacetate (NSC 3039) on ovarian carcinoma cells in vitro. Cancer Res. 1997 Oct 1;57(19):4309–15.
Ferrandina, G., et al. “Growth inhibitory effects of sodium phenylacetate (NSC 3039) on ovarian carcinoma cells in vitro.Cancer Res, vol. 57, no. 19, Oct. 1997, pp. 4309–15.
Ferrandina G, Melichar B, Loercher A, Verschraegen CF, Kudelka AP, Edwards CL, Scambia G, Kavanagh JJ, Abbruzzese JL, Freedman RS. Growth inhibitory effects of sodium phenylacetate (NSC 3039) on ovarian carcinoma cells in vitro. Cancer Res. 1997 Oct 1;57(19):4309–4315.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

October 1, 1997

Volume

57

Issue

19

Start / End Page

4309 / 4315

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Phenylacetates
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Humans
  • Growth Inhibitors
  • Female
  • Dose-Response Relationship, Drug
  • Cystadenocarcinoma, Serous
  • Cisplatin