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Human serum-derived hydroxy long-chain fatty acids exhibit anti-inflammatory and anti-proliferative activity.

Ritchie SA, Jayasinghe D, Davies GF, Ahiahonu P, Ma H, Goodenowe DB - J. Exp. Clin. Cancer Res. (2011)

Bottom Line: Enriched fractions resulted in poly-ADP ribose polymerase (PARP) cleavage, suppression of NFκB, induction of IκBα, and reduction in NOS2 mRNA transcript levels.Our results show that human serum extracts enriched with endogenous long-chain hydroxy fatty acids possess anti-inflammatory and anti-proliferative activity.These findings support a hypothesis that the reduction of these metabolites with age may result in a compromised ability to defend against uncontrolled cell growth and inflammation, and could therefore represent a significant risk for the development of CRC.

View Article: PubMed Central - HTML - PubMed

Affiliation: Phenomenome Discoveries, Inc, Saskatoon, Saskatchewan, Canada. s.ritchie@phenomenome.com

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TNFα response in RAW264.7 cells treated with GTA+ve and GTA-ve extracts. RAW264.7 cells were pre-treated for 4 hours with GTA+ve or GTA-ve extracts followed by the addition of LPS (1 ug/ml) for 20 hours. (A) TNFα mRNA transcripts as determined by real-time rtPCR, (B) TNFα relative protein levels in cell lysates following 80 ug/ml treatment, and (C) TNFα protein levels in conditioned media as determined by ELISA. Asterisks indicate p < 0.05 relative to LPS treatment alone. Data are expressed as the average of three duplicate experiments ± 1S.D.
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Figure 7: TNFα response in RAW264.7 cells treated with GTA+ve and GTA-ve extracts. RAW264.7 cells were pre-treated for 4 hours with GTA+ve or GTA-ve extracts followed by the addition of LPS (1 ug/ml) for 20 hours. (A) TNFα mRNA transcripts as determined by real-time rtPCR, (B) TNFα relative protein levels in cell lysates following 80 ug/ml treatment, and (C) TNFα protein levels in conditioned media as determined by ELISA. Asterisks indicate p < 0.05 relative to LPS treatment alone. Data are expressed as the average of three duplicate experiments ± 1S.D.

Mentions: Similar effects were observed with TNFα upon treatment with GTA+ve extract, which showed significantly reduced mRNA transcript levels (p < 0.05, Figure 7A) as well as protein levels in cell lysates and conditioned media (Figures 7B and 7C, respectively). Consistent with the above findings, transcript levels of COX2 and IL-1β (Figures 8A and 8B), as well as IL-1β protein levels (Figure 8C), were also significantly reduced (p < 0.05) with GTA+ve treatment. The results indicate that human blood extracts containing GTAs have anti-proliferative and anti-inflammatory properties that GTA-ve extracts lack.


Human serum-derived hydroxy long-chain fatty acids exhibit anti-inflammatory and anti-proliferative activity.

Ritchie SA, Jayasinghe D, Davies GF, Ahiahonu P, Ma H, Goodenowe DB - J. Exp. Clin. Cancer Res. (2011)

TNFα response in RAW264.7 cells treated with GTA+ve and GTA-ve extracts. RAW264.7 cells were pre-treated for 4 hours with GTA+ve or GTA-ve extracts followed by the addition of LPS (1 ug/ml) for 20 hours. (A) TNFα mRNA transcripts as determined by real-time rtPCR, (B) TNFα relative protein levels in cell lysates following 80 ug/ml treatment, and (C) TNFα protein levels in conditioned media as determined by ELISA. Asterisks indicate p < 0.05 relative to LPS treatment alone. Data are expressed as the average of three duplicate experiments ± 1S.D.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3108922&req=5

Figure 7: TNFα response in RAW264.7 cells treated with GTA+ve and GTA-ve extracts. RAW264.7 cells were pre-treated for 4 hours with GTA+ve or GTA-ve extracts followed by the addition of LPS (1 ug/ml) for 20 hours. (A) TNFα mRNA transcripts as determined by real-time rtPCR, (B) TNFα relative protein levels in cell lysates following 80 ug/ml treatment, and (C) TNFα protein levels in conditioned media as determined by ELISA. Asterisks indicate p < 0.05 relative to LPS treatment alone. Data are expressed as the average of three duplicate experiments ± 1S.D.
Mentions: Similar effects were observed with TNFα upon treatment with GTA+ve extract, which showed significantly reduced mRNA transcript levels (p < 0.05, Figure 7A) as well as protein levels in cell lysates and conditioned media (Figures 7B and 7C, respectively). Consistent with the above findings, transcript levels of COX2 and IL-1β (Figures 8A and 8B), as well as IL-1β protein levels (Figure 8C), were also significantly reduced (p < 0.05) with GTA+ve treatment. The results indicate that human blood extracts containing GTAs have anti-proliferative and anti-inflammatory properties that GTA-ve extracts lack.

Bottom Line: Enriched fractions resulted in poly-ADP ribose polymerase (PARP) cleavage, suppression of NFκB, induction of IκBα, and reduction in NOS2 mRNA transcript levels.Our results show that human serum extracts enriched with endogenous long-chain hydroxy fatty acids possess anti-inflammatory and anti-proliferative activity.These findings support a hypothesis that the reduction of these metabolites with age may result in a compromised ability to defend against uncontrolled cell growth and inflammation, and could therefore represent a significant risk for the development of CRC.

View Article: PubMed Central - HTML - PubMed

Affiliation: Phenomenome Discoveries, Inc, Saskatoon, Saskatchewan, Canada. s.ritchie@phenomenome.com

Show MeSH
Related in: MedlinePlus