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

Peiying Yang, Peter Collin, Timothy Madden, Diana Chan, Bridget Sweeney-Gotsch, David McConkey, Robert A. Newman

Research output: Contribution to journalArticle

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 μg/ml. PI staining clearly showed that 12-MTA caused PC3 cell death through induction of apoptosis. At 50 μg/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 μg/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.

Original languageEnglish (US)
Pages (from-to)281-291
Number of pages11
JournalProstate
Volume55
Issue number4
DOIs
StatePublished - Jun 1 2003
Externally publishedYes

Fingerprint

Arachidonate 5-Lipoxygenase
Fatty Acids
Cell Proliferation
Caspase 3
Propidium
Neoplasms
Apoptosis
Prostatic Neoplasms
aseanostatin P5
Cell Death
Sea Cucumbers
Fatty Alcohols
Staining and Labeling
Lipoxygenase
Eicosanoids
Prostaglandin-Endoperoxide Synthases

Keywords

  • 12-methyltetradecanoic acid
  • 5-lipoxygenase
  • Apoptosis
  • Prostate cancer cells

ASJC Scopus subject areas

  • Urology

Cite this

Inhibition of proliferation of PC3 cells by the branched-chain fatty acid, 12-methyltetradecanoic acid, is associated with inhibition of 5-lipoxygenase. / Yang, Peiying; Collin, Peter; Madden, Timothy; Chan, Diana; Sweeney-Gotsch, Bridget; McConkey, David; Newman, Robert A.

In: Prostate, Vol. 55, No. 4, 01.06.2003, p. 281-291.

Research output: Contribution to journalArticle

Yang, Peiying ; Collin, Peter ; Madden, Timothy ; Chan, Diana ; Sweeney-Gotsch, Bridget ; McConkey, David ; Newman, Robert A. / Inhibition of proliferation of PC3 cells by the branched-chain fatty acid, 12-methyltetradecanoic acid, is associated with inhibition of 5-lipoxygenase. In: Prostate. 2003 ; Vol. 55, No. 4. pp. 281-291.
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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 μg/ml. PI staining clearly showed that 12-MTA caused PC3 cell death through induction of apoptosis. At 50 μg/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 μg/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.",
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T1 - Inhibition of proliferation of PC3 cells by the branched-chain fatty acid, 12-methyltetradecanoic acid, is associated with inhibition of 5-lipoxygenase

AU - Yang, Peiying

AU - Collin, Peter

AU - Madden, Timothy

AU - Chan, Diana

AU - Sweeney-Gotsch, Bridget

AU - McConkey, David

AU - Newman, Robert A.

PY - 2003/6/1

Y1 - 2003/6/1

N2 - 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 μg/ml. PI staining clearly showed that 12-MTA caused PC3 cell death through induction of apoptosis. At 50 μg/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 μg/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.

AB - 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 μg/ml. PI staining clearly showed that 12-MTA caused PC3 cell death through induction of apoptosis. At 50 μg/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 μg/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.

KW - 12-methyltetradecanoic acid

KW - 5-lipoxygenase

KW - Apoptosis

KW - Prostate cancer cells

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