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Arachidonic acid may be cause of cancer regardless of its metabolites.
Arachidonic acid may be cause of cancer regardless of its metabolites.
How much longer will the ludicrous "essential fatty acid" claim
persist, in light of the actual evidence?
Mol Cancer Res. 2008 Apr;6(4):535-45.
"Arachidonic Acid-induced Ca2+ entry is involved in early steps of
tumor angiogenesis."
Fiorio Pla A, Grange C, Antoniotti S, Tomatis C, Merlino A, Bussolati
B, Munaron L.
Department of Animal and Human Biology, University of Torino, Via
Accademia Albertina 13, 10123 Turin, Italy.
alessandra.fiorio@unito,it .
Growth factor-induced intracellular calcium signals in endothelial
cells regulate cytosolic and nuclear events involved in the angiogenic
process. Among the intracellular messengers released after
proangiogenic stimulation, arachidonic acid (AA) plays a key role and
its effects are strictly related to calcium homeostasis and cell
proliferation. Here, we studied AA-induced intracellular calcium
signals in endothelial cells derived from human breast carcinomas (B-
TEC). AA promotes B-TEC proliferation and organization of vessel-like
structures in vitro. The effect is directly mediated by the fatty acid
without a significant contribution of its metabolites. AA induces
Ca(2+)(i) signals in the entire capillary-like structure during the
early phases of tubulogenesis in vitro. No such responses are
detectable in B-TECs organized in more structured tubules. In B-TECs
growing in monolayer, AA induces two different signals: a Ca(2+)(i)
increase due to Ca(2+) entry and an inhibition of store-dependent
Ca(2+) entry induced by thapsigargin or ATP. An inhibitor of Ca(2+)
entry and angiogenesis, carboxyamidotriazole, significantly and
specifically decreases AA-induced B-TEC tubulogenesis, as well as AA-
induced Ca(2+) signals in B-TECs. We conclude that (a) AA-activated
Ca(2+) entry is associated with the progression through the early
phases of angiogenesis, mainly involving proliferation and
tubulogenesis, and it is down-regulated during the reorganization of
tumor-derived endothelial cells in capillary-like structures; and (b)
inhibition of AA-induced Ca(2+) entry may contribute to the
antiangiogenic action of carboxyamidotriazole. (Mol Cancer Res
2008;6(4):535-45).
How much longer will the ludicrous "essential fatty acid" claim
persist, in light of the actual evidence?
Mol Cancer Res. 2008 Apr;6(4):535-45.
"Arachidonic Acid-induced Ca2+ entry is involved in early steps of
tumor angiogenesis."
Fiorio Pla A, Grange C, Antoniotti S, Tomatis C, Merlino A, Bussolati
B, Munaron L.
Department of Animal and Human Biology, University of Torino, Via
Accademia Albertina 13, 10123 Turin, Italy.
alessandra.fiorio@unito,it .
Growth factor-induced intracellular calcium signals in endothelial
cells regulate cytosolic and nuclear events involved in the angiogenic
process. Among the intracellular messengers released after
proangiogenic stimulation, arachidonic acid (AA) plays a key role and
its effects are strictly related to calcium homeostasis and cell
proliferation. Here, we studied AA-induced intracellular calcium
signals in endothelial cells derived from human breast carcinomas (B-
TEC). AA promotes B-TEC proliferation and organization of vessel-like
structures in vitro. The effect is directly mediated by the fatty acid
without a significant contribution of its metabolites. AA induces
Ca(2+)(i) signals in the entire capillary-like structure during the
early phases of tubulogenesis in vitro. No such responses are
detectable in B-TECs organized in more structured tubules. In B-TECs
growing in monolayer, AA induces two different signals: a Ca(2+)(i)
increase due to Ca(2+) entry and an inhibition of store-dependent
Ca(2+) entry induced by thapsigargin or ATP. An inhibitor of Ca(2+)
entry and angiogenesis, carboxyamidotriazole, significantly and
specifically decreases AA-induced B-TEC tubulogenesis, as well as AA-
induced Ca(2+) signals in B-TECs. We conclude that (a) AA-activated
Ca(2+) entry is associated with the progression through the early
phases of angiogenesis, mainly involving proliferation and
tubulogenesis, and it is down-regulated during the reorganization of
tumor-derived endothelial cells in capillary-like structures; and (b)
inhibition of AA-induced Ca(2+) entry may contribute to the
antiangiogenic action of carboxyamidotriazole. (Mol Cancer Res
2008;6(4):535-45).
