Clinical Cancer Research, Vol 4, Issue 12 3069-3076, Copyright © 1998 by American Association for Cancer Research

ARTICLES

Growth inhibitory effects of aromatic fatty acids on ovarian tumor cell lines [published erratum appears in Clin Cancer Res 1999 Feb;5(2):478]

B Melichar, G Ferrandina, CF Verschraegen, A Loercher, JL Abbruzzese and RS Freedman
Department of Gynecologic Oncology, The University of Texas, M. D. Anderson Cancer Center, Houston 77030, USA.

Epithelial ovarian cancer is a major cause of cancer-related mortality in women, making the search for new treatment modalities essential. Sodium phenylacetate (NaPa), a phenylalanine derivative, has been shown to induce cytostasis and differentiation by inhibiting protein isoprenylation. Similar effects have been observed with phenylbutyrate, a phenylacetate congener. We examined in parallel the growth inhibitory activity against human ovarian carcinoma cell lines of phenylacetate, phenylbutyric acid (PB), and certain related compounds, and comparisons were made with lovastatin. On a molar basis, hydroxykynurenine and kynurenine showed the highest activity followed by PB and NaPa. Ovarian carcinoma cell lines were also sensitive to lovastatin in micromolar concentrations. Additive effects were observed when PB was combined with cisplatin or when NaPa or PB were combined with lovastatin. NaPa and PB, but not kynurenine, inhibited incorporation of [3H]mevalonate into ovarian carcinoma cells. An immune modulatory role might also be suggested for PB because it resulted in increased ovarian tumor cell expression of human leukocyte antigen class I and the cluster of differentiation molecule CD58, whereas transforming growth factor-beta2 expression was decreased. Phenylbutyrate, which is the ester form of PB, has shown acceptable pharmacological properties and clinical responses in patients with other malignancies, and might be considered for evaluation in ovarian cancer.

This article has been cited by other articles:

				K. A. Strait, B. Dabbas, E. H. Hammond, C. T. Warnick, S. J. Ilstrup, and C. D. Ford Cell Cycle Blockade and Differentiation of Ovarian Cancer Cells by the Histone Deacetylase Inhibitor Trichostatin A Are Associated with Changes in p21, Rb, and Id Proteins Mol. Cancer Ther., November 1, 2002; 1(13): 1181 - 1190. [Abstract] [Full Text] [PDF]

				A. Faggiotto and R. Paoletti Statins and Blockers of the Renin-Angiotensin System : Vascular Protection Beyond Their Primary Mode of Action Hypertension, October 1, 1999; 34(4): 987 - 996. [Abstract] [Full Text] [PDF]

				M. E. Gordinier, H.-Z. Zhang, R. Patenia, L. B. Levy, E. N. Atkinson, M. A. Nash, R. L. Katz, C. D. Platsoucas, and R. S. Freedman Quantitative Analysis of Transforming Growth Factor {beta}1 and 2 in Ovarian Carcinoma Clin. Cancer Res., September 1, 1999; 5(9): 2498 - 2505. [Abstract] [Full Text] [PDF]