Proteomics Study Reveals That Docosahexaenoic and Arachidonic Acids Exert Different <i>In Vitro</i> Anticancer Activities in Colorectal Cancer Cells

Two polyunsaturated fatty acids, docosahexaenoic acid (DHA) and arachidonic acid (ARA), as well as derivatives, such as eicosanoids, regulate different activities, affecting transcription factors and, therefore, DNA transcription, being a critical step for the functioning of fatty-acid-derived signaling. This work has attempted to determine the <i>in vitro</i> anticancer activities of these molecules linked to the gene transcription regulation of HT-29 colorectal cancer cells. We applied the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test along with lactate dehydrogenase and caspase-3 assays; proteome changes were assessed by “sequential windowed acquisition of all theoretical mass spectra” quantitative proteomics, followed by pathway analysis, to determine the affected molecular mechanisms. In all assays, DHA inhibited cell proliferation of HT-29 cells to a higher extent than ARA and acted primarily by downregulating proteasome particles, while ARA presented a dramatic effect on all six DNA replication helicase particles. The results indicated that both DHA and ARA are potential chemopreventive agent candidates

Proteomics Study Reveals That Docosahexaenoic and Arachidonic Acids Exert Different <i>In Vitro</i> Anticancer Activities in Colorectal Cancer Cells

Two polyunsaturated fatty acids, docosahexaenoic acid (DHA) and arachidonic acid (ARA), as well as derivatives, such as eicosanoids, regulate different activities, affecting transcription factors and, therefore, DNA transcription, being a critical step for the functioning of fatty-acid-derived signaling. This work has attempted to determine the <i>in vitro</i> anticancer activities of these molecules linked to the gene transcription regulation of HT-29 colorectal cancer cells. We applied the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test along with lactate dehydrogenase and caspase-3 assays; proteome changes were assessed by “sequential windowed acquisition of all theoretical mass spectra” quantitative proteomics, followed by pathway analysis, to determine the affected molecular mechanisms. In all assays, DHA inhibited cell proliferation of HT-29 cells to a higher extent than ARA and acted primarily by downregulating proteasome particles, while ARA presented a dramatic effect on all six DNA replication helicase particles. The results indicated that both DHA and ARA are potential chemopreventive agent candidates

Proteomics Study Reveals That Docosahexaenoic and Arachidonic Acids Exert Different <i>In Vitro</i> Anticancer Activities in Colorectal Cancer Cells

Two polyunsaturated fatty acids, docosahexaenoic acid (DHA) and arachidonic acid (ARA), as well as derivatives, such as eicosanoids, regulate different activities, affecting transcription factors and, therefore, DNA transcription, being a critical step for the functioning of fatty-acid-derived signaling. This work has attempted to determine the <i>in vitro</i> anticancer activities of these molecules linked to the gene transcription regulation of HT-29 colorectal cancer cells. We applied the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test along with lactate dehydrogenase and caspase-3 assays; proteome changes were assessed by “sequential windowed acquisition of all theoretical mass spectra” quantitative proteomics, followed by pathway analysis, to determine the affected molecular mechanisms. In all assays, DHA inhibited cell proliferation of HT-29 cells to a higher extent than ARA and acted primarily by downregulating proteasome particles, while ARA presented a dramatic effect on all six DNA replication helicase particles. The results indicated that both DHA and ARA are potential chemopreventive agent candidates

Proteomics Study Reveals That Docosahexaenoic and Arachidonic Acids Exert Different <i>In Vitro</i> Anticancer Activities in Colorectal Cancer Cells

Two polyunsaturated fatty acids, docosahexaenoic acid (DHA) and arachidonic acid (ARA), as well as derivatives, such as eicosanoids, regulate different activities, affecting transcription factors and, therefore, DNA transcription, being a critical step for the functioning of fatty-acid-derived signaling. This work has attempted to determine the <i>in vitro</i> anticancer activities of these molecules linked to the gene transcription regulation of HT-29 colorectal cancer cells. We applied the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test along with lactate dehydrogenase and caspase-3 assays; proteome changes were assessed by “sequential windowed acquisition of all theoretical mass spectra” quantitative proteomics, followed by pathway analysis, to determine the affected molecular mechanisms. In all assays, DHA inhibited cell proliferation of HT-29 cells to a higher extent than ARA and acted primarily by downregulating proteasome particles, while ARA presented a dramatic effect on all six DNA replication helicase particles. The results indicated that both DHA and ARA are potential chemopreventive agent candidates

Proteomics Study Reveals That Docosahexaenoic and Arachidonic Acids Exert Different <i>In Vitro</i> Anticancer Activities in Colorectal Cancer Cells

Two polyunsaturated fatty acids, docosahexaenoic acid (DHA) and arachidonic acid (ARA), as well as derivatives, such as eicosanoids, regulate different activities, affecting transcription factors and, therefore, DNA transcription, being a critical step for the functioning of fatty-acid-derived signaling. This work has attempted to determine the <i>in vitro</i> anticancer activities of these molecules linked to the gene transcription regulation of HT-29 colorectal cancer cells. We applied the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test along with lactate dehydrogenase and caspase-3 assays; proteome changes were assessed by “sequential windowed acquisition of all theoretical mass spectra” quantitative proteomics, followed by pathway analysis, to determine the affected molecular mechanisms. In all assays, DHA inhibited cell proliferation of HT-29 cells to a higher extent than ARA and acted primarily by downregulating proteasome particles, while ARA presented a dramatic effect on all six DNA replication helicase particles. The results indicated that both DHA and ARA are potential chemopreventive agent candidates

Approximate original fatty acid profiles calculated for frozen mammals.

<p>^a Only the major FAs have been considered.</p><p>^b A superscript number indicates the FA percentages found in frozen samples, while all derived percentages appear in italics. In reconstructed figures, C18 PUFA percentages are partially subtracted from PA figures; C20 PUFAs from EA. For both bison, reconstructed OA percentages are partially subtracted from PA.</p><p>^c PUFA ratios and PA percentage in agreement with those of grass-fed elephants <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084480#pone.0084480-Meyer1" target="_blank">[19]</a>.</p><p>^d PUFA ratios and PA percentage as grass-fed Siberian <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084480#pone.0084480-Mordovskaya1" target="_blank">[20]</a> and Galician horses <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084480#pone.0084480-GuilGuerrero1" target="_blank">[21]</a>.</p><p>^e PUFA ratios and PA percentage as grass-fed Bison subcutaneous fat <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084480#pone.0084480-Turner1" target="_blank">[22]</a>.</p

Unsaturated fatty acids composition of the fat from frozen mammals^a.

<p>^a Mean ± SD of three independent determinations performed by GLC-MS.</p

Total fatty acids and saturated fatty acids composition of the fat from frozen mammals ^a.

<p>^a Mean ± SD of three independent determinations performed by GLC-MS.</p