Conjugated linoleic acids (CLA's) decrease prostate cancer cell proliferation: different molecular mechanisms for cis-9, trans-11 and trans-10, cis-12 isomers

J J Ochoa, A J Farquharson, I Grant, L E Moffat, S D Heys, K W J Wahle

Research output: Contribution to journalArticle

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Abstract

The aims of this study were to examine the anti-proliferative effects of different concentrations of a commercial preparation of conjugated linoleic acids (CLA) mixture of isomers [cis-9, trans-11 CLA (c9,t11 CLA): trans-10, cis-12 CLA (50:50)] and their constituent isomers on PC-3, a human prostatic carcinoma cell line, and to study their effects on gene expression (mRNA and protein levels) of different enzymes and oncoproteins involved in oncogenesis and progression of prostate cancer. This includes pathways for arachidonic acid metabolism [cyclooxygenase 1 (COX-1), 2 (COX-2) and 5-lipoxygenase (5-LOX)], apoptosis (bcl-2) and cell cycle control (p21(WAF/Cip1)). Our results indicate a significant decrease in PC-3 proliferation elicited by CLA, although with high variability between isomers. The trans-10, cis-12 CLA was the most effective isomer (55% inhibition). This isomer was also able to decrease bcl-2 gene expression and to increase p21(WAF1/Cip1) mRNA levels (60% increase at highest concentration). In contrast, cis-9, trans-11 had no effect on these proteins but had a clear effect on 5-LOX expression and to a lesser degree on COX-2 protein level isomers. In conclusion, the anti-proliferative effects on PC-3 of CLA mixture and their constituent isomers are not equivalent, due to the different pathways involved for individual isomers. Trans-10, cis-12 seems to work preferentially through modulation of apoptosis and cell cycle control, while c9,t11 CLA isomer affects arachidonic acid metabolism.

Original languageEnglish
Pages (from-to)1185-1191
Number of pages7
JournalCarcinogenesis
Volume25
Issue number7
Early online date19 Feb 2004
DOIs
Publication statusPublished - Jul 2004

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Conjugated Linoleic Acids
Arachidonate 5-Lipoxygenase
Prostatic Neoplasms
Cell Proliferation
Cell Cycle Checkpoints
Apoptosis
bcl-2 Genes
Gene Expression
Cyclooxygenase 1
Messenger RNA
Proteins
Oncogene Proteins
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases
Arachidonic Acid
Carcinogenesis
Carcinoma
Cell Line
Enzymes
trans-10,cis-12-conjugated linoleic acid

Keywords

  • BIOLOGICALLY-ACTIVE ISOMERS
  • APOPTOSIS
  • CYCLOOXYGENASE-2
  • PREVENTION
  • INHIBITION
  • EXPRESSION
  • CARCINOMA
  • GROWTH
  • HEALTH
  • FUTURE

Cite this

Conjugated linoleic acids (CLA's) decrease prostate cancer cell proliferation: different molecular mechanisms for cis-9, trans-11 and trans-10, cis-12 isomers. / Ochoa, J J ; Farquharson, A J ; Grant, I ; Moffat, L E ; Heys, S D ; Wahle, K W J .

In: Carcinogenesis, Vol. 25, No. 7, 07.2004, p. 1185-1191.

Research output: Contribution to journalArticle

Ochoa, J J ; Farquharson, A J ; Grant, I ; Moffat, L E ; Heys, S D ; Wahle, K W J . / Conjugated linoleic acids (CLA's) decrease prostate cancer cell proliferation: different molecular mechanisms for cis-9, trans-11 and trans-10, cis-12 isomers. In: Carcinogenesis. 2004 ; Vol. 25, No. 7. pp. 1185-1191.
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abstract = "The aims of this study were to examine the anti-proliferative effects of different concentrations of a commercial preparation of conjugated linoleic acids (CLA) mixture of isomers [cis-9, trans-11 CLA (c9,t11 CLA): trans-10, cis-12 CLA (50:50)] and their constituent isomers on PC-3, a human prostatic carcinoma cell line, and to study their effects on gene expression (mRNA and protein levels) of different enzymes and oncoproteins involved in oncogenesis and progression of prostate cancer. This includes pathways for arachidonic acid metabolism [cyclooxygenase 1 (COX-1), 2 (COX-2) and 5-lipoxygenase (5-LOX)], apoptosis (bcl-2) and cell cycle control (p21(WAF/Cip1)). Our results indicate a significant decrease in PC-3 proliferation elicited by CLA, although with high variability between isomers. The trans-10, cis-12 CLA was the most effective isomer (55{\%} inhibition). This isomer was also able to decrease bcl-2 gene expression and to increase p21(WAF1/Cip1) mRNA levels (60{\%} increase at highest concentration). In contrast, cis-9, trans-11 had no effect on these proteins but had a clear effect on 5-LOX expression and to a lesser degree on COX-2 protein level isomers. In conclusion, the anti-proliferative effects on PC-3 of CLA mixture and their constituent isomers are not equivalent, due to the different pathways involved for individual isomers. Trans-10, cis-12 seems to work preferentially through modulation of apoptosis and cell cycle control, while c9,t11 CLA isomer affects arachidonic acid metabolism.",
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TY - JOUR

T1 - Conjugated linoleic acids (CLA's) decrease prostate cancer cell proliferation: different molecular mechanisms for cis-9, trans-11 and trans-10, cis-12 isomers

AU - Ochoa, J J

AU - Farquharson, A J

AU - Grant, I

AU - Moffat, L E

AU - Heys, S D

AU - Wahle, K W J

PY - 2004/7

Y1 - 2004/7

N2 - The aims of this study were to examine the anti-proliferative effects of different concentrations of a commercial preparation of conjugated linoleic acids (CLA) mixture of isomers [cis-9, trans-11 CLA (c9,t11 CLA): trans-10, cis-12 CLA (50:50)] and their constituent isomers on PC-3, a human prostatic carcinoma cell line, and to study their effects on gene expression (mRNA and protein levels) of different enzymes and oncoproteins involved in oncogenesis and progression of prostate cancer. This includes pathways for arachidonic acid metabolism [cyclooxygenase 1 (COX-1), 2 (COX-2) and 5-lipoxygenase (5-LOX)], apoptosis (bcl-2) and cell cycle control (p21(WAF/Cip1)). Our results indicate a significant decrease in PC-3 proliferation elicited by CLA, although with high variability between isomers. The trans-10, cis-12 CLA was the most effective isomer (55% inhibition). This isomer was also able to decrease bcl-2 gene expression and to increase p21(WAF1/Cip1) mRNA levels (60% increase at highest concentration). In contrast, cis-9, trans-11 had no effect on these proteins but had a clear effect on 5-LOX expression and to a lesser degree on COX-2 protein level isomers. In conclusion, the anti-proliferative effects on PC-3 of CLA mixture and their constituent isomers are not equivalent, due to the different pathways involved for individual isomers. Trans-10, cis-12 seems to work preferentially through modulation of apoptosis and cell cycle control, while c9,t11 CLA isomer affects arachidonic acid metabolism.

AB - The aims of this study were to examine the anti-proliferative effects of different concentrations of a commercial preparation of conjugated linoleic acids (CLA) mixture of isomers [cis-9, trans-11 CLA (c9,t11 CLA): trans-10, cis-12 CLA (50:50)] and their constituent isomers on PC-3, a human prostatic carcinoma cell line, and to study their effects on gene expression (mRNA and protein levels) of different enzymes and oncoproteins involved in oncogenesis and progression of prostate cancer. This includes pathways for arachidonic acid metabolism [cyclooxygenase 1 (COX-1), 2 (COX-2) and 5-lipoxygenase (5-LOX)], apoptosis (bcl-2) and cell cycle control (p21(WAF/Cip1)). Our results indicate a significant decrease in PC-3 proliferation elicited by CLA, although with high variability between isomers. The trans-10, cis-12 CLA was the most effective isomer (55% inhibition). This isomer was also able to decrease bcl-2 gene expression and to increase p21(WAF1/Cip1) mRNA levels (60% increase at highest concentration). In contrast, cis-9, trans-11 had no effect on these proteins but had a clear effect on 5-LOX expression and to a lesser degree on COX-2 protein level isomers. In conclusion, the anti-proliferative effects on PC-3 of CLA mixture and their constituent isomers are not equivalent, due to the different pathways involved for individual isomers. Trans-10, cis-12 seems to work preferentially through modulation of apoptosis and cell cycle control, while c9,t11 CLA isomer affects arachidonic acid metabolism.

KW - BIOLOGICALLY-ACTIVE ISOMERS

KW - APOPTOSIS

KW - CYCLOOXYGENASE-2

KW - PREVENTION

KW - INHIBITION

KW - EXPRESSION

KW - CARCINOMA

KW - GROWTH

KW - HEALTH

KW - FUTURE

U2 - 10.1093/CARCIN/BGH116

DO - 10.1093/CARCIN/BGH116

M3 - Article

VL - 25

SP - 1185

EP - 1191

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 7

ER -