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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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Related in: MedlinePlus

Proliferation of SW620 cells treated with GTA+ve and GTA-ve extracts. (A) SW620 cells were incubated with increasing concentrations of GTA+ve and GTA-ve extracts for 24 hours and proliferation assayed by MTT. (B) The 80 ug/ml concentration of GTA+ve and GTA-ve extracts was then used to treat cells for up to 48 hours and the effect on cell proliferation assayed by MTT. Data are expressed as percent of vehicle or 0 hrs ± 1S.D. (C) Representative Western blot analysis of caspase-mediated PARP cleavage fragments resulting from treatment with GTA+ve and -ve extracts. Experiments were repeated at least three times.
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Figure 3: Proliferation of SW620 cells treated with GTA+ve and GTA-ve extracts. (A) SW620 cells were incubated with increasing concentrations of GTA+ve and GTA-ve extracts for 24 hours and proliferation assayed by MTT. (B) The 80 ug/ml concentration of GTA+ve and GTA-ve extracts was then used to treat cells for up to 48 hours and the effect on cell proliferation assayed by MTT. Data are expressed as percent of vehicle or 0 hrs ± 1S.D. (C) Representative Western blot analysis of caspase-mediated PARP cleavage fragments resulting from treatment with GTA+ve and -ve extracts. Experiments were repeated at least three times.

Mentions: We determined whether the enriched GTA+ve fraction had any effects on cell viability compared to the GTA-ve fraction by treating SW620 cells for 24 hrs with three concentrations of each fraction and measuring the effect on cell proliferation by MTT assay. The GTA+ve fraction showed a 40% reduction in cell viability at a dose of 80 ug/ml (Figure 3A) while GTA-ve treatment had no effect. Treatment up to 48 hrs using 80 ug/ml showed the same 40% reduction as early as 12 hrs, which dropped further to 70% by 48 hrs (Figure 3B). No effect on cell proliferation was observed with the GTA-ve fraction or vehicle (DMSO). Evidence of apoptotic activity was determined by the detection of poly(ADP-ribose) polymerase (PARP) cleavage products through Western blot (Figure 3C). A number of PARP cleavage products including the hallmark 89 and 24 kDa fragments, as well as others (Figure 3C), were induced following 48 hrs treatment with GTA+ve fraction, but not with GTA-ve treatment, suggesting a possible pro-apoptotic function of GTAs.


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)

Proliferation of SW620 cells treated with GTA+ve and GTA-ve extracts. (A) SW620 cells were incubated with increasing concentrations of GTA+ve and GTA-ve extracts for 24 hours and proliferation assayed by MTT. (B) The 80 ug/ml concentration of GTA+ve and GTA-ve extracts was then used to treat cells for up to 48 hours and the effect on cell proliferation assayed by MTT. Data are expressed as percent of vehicle or 0 hrs ± 1S.D. (C) Representative Western blot analysis of caspase-mediated PARP cleavage fragments resulting from treatment with GTA+ve and -ve extracts. Experiments were repeated at least three times.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Proliferation of SW620 cells treated with GTA+ve and GTA-ve extracts. (A) SW620 cells were incubated with increasing concentrations of GTA+ve and GTA-ve extracts for 24 hours and proliferation assayed by MTT. (B) The 80 ug/ml concentration of GTA+ve and GTA-ve extracts was then used to treat cells for up to 48 hours and the effect on cell proliferation assayed by MTT. Data are expressed as percent of vehicle or 0 hrs ± 1S.D. (C) Representative Western blot analysis of caspase-mediated PARP cleavage fragments resulting from treatment with GTA+ve and -ve extracts. Experiments were repeated at least three times.
Mentions: We determined whether the enriched GTA+ve fraction had any effects on cell viability compared to the GTA-ve fraction by treating SW620 cells for 24 hrs with three concentrations of each fraction and measuring the effect on cell proliferation by MTT assay. The GTA+ve fraction showed a 40% reduction in cell viability at a dose of 80 ug/ml (Figure 3A) while GTA-ve treatment had no effect. Treatment up to 48 hrs using 80 ug/ml showed the same 40% reduction as early as 12 hrs, which dropped further to 70% by 48 hrs (Figure 3B). No effect on cell proliferation was observed with the GTA-ve fraction or vehicle (DMSO). Evidence of apoptotic activity was determined by the detection of poly(ADP-ribose) polymerase (PARP) cleavage products through Western blot (Figure 3C). A number of PARP cleavage products including the hallmark 89 and 24 kDa fragments, as well as others (Figure 3C), were induced following 48 hrs treatment with GTA+ve fraction, but not with GTA-ve treatment, suggesting a possible pro-apoptotic function of GTAs.

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