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Prostate. 2003 Jun 1;55(4):281-91.

Inhibition of proliferation of PC3 cells by the branched-chain fatty acid, 12-methyltetradecanoic acid, is associated with inhibition of 5-lipoxygenase.

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  • 1Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77090-1009, USA.

Abstract

BACKGROUND:

Branched-chain fatty acids or fatty alcohols have been reported to possess anti-tumor activity in various tumor models. Here we study 12-methyltetradecanoic acid (12-MTA), a branched-chain fatty acid, isolated from a sea cucumber extract, on the growth of prostate cancer cells and investigate the underlying mechanisms of its effect.

METHODS:

12-MTA was evaluated by MTT assay for its ability to inhibit cell proliferation in various cancer types. The ability of 12-MTA to induce apoptosis of PC3 cells was examined by morphologic changes, propidium iodide (PI) staining, and caspase-3 activation. Furthermore, alteration of eicosanoid metabolism by 12-MTA was examined in PC3 and RBL-1 cells and in purified lipoxygenase (LOX) and cyclooxygenase (COX) enzymes.

RESULTS:

12-MTA inhibited proliferation of various cell lines, with IC50s ranging from 17.99 to 35.44 microg/ml. PI staining clearly showed that 12-MTA caused PC3 cell death through induction of apoptosis. At 50 microg/ml, 12-MTA increased caspase-3 activity four to seven-fold compared with that in control cells. Examination of cellular arachidonate metabolism showed that at 25 microg/ml, 12-MTA reduced the level of 5-hydroxyeicosatetraenoic acid (5-HETE) by 45%. Furthermore, exogenous 5-HETE protects PC3 cells from 12-MTA induced cell death.

CONCLUSIONS:

12-MTA inhibited proliferation of cancer cells via apoptosis, in which caspase-3 may play a role. At relevant concentrations, 12-MTA can selectively inhibit the formation of 5-HETE, a metabolite of 5-lipoxygenase. This agent may be a novel adjunctive therapy for selected malignancies including prostate cancer.

Copyright 2003 Wiley-Liss, Inc.

PMID:
12712407
[PubMed - indexed for MEDLINE]
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