Arachidonic Acid Induces Apoptosis Under Serum- Free Conditions by Blocking PAK1-Mediated PUMA Suppression

Ko S, Woo TG, Lee SH, Ha NC and Park BJ

Department of Molecular Biology, College of Natural Science, Pusan National University, Republic of Korea
Department of Food Science, College of Agricultural and Life Sciences, Seoul National University, Republic of Korea
These authors contributed equally to this work

^*Correspondance to: Bum-Joon Park 

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Abstract:

Arachidonic acid is an essential lipid, which should be supplied by food uptake or biosynthetic pathway. In addition, it can be converted into Prostaglandin E2 (PGE2) by COX-2, which is well known to be related with inflammation as well as cancer development. In fact, treatment of PGE2 can induce colon adenoma and COX-2 expression is elevated in colon cancers. However, the relevance between arachidonic acid itself and cancer has not been investigated. Here we provided evidences that arachidonic acid can induce cell death via inhibition of PAK1-PUMA binding. Since serum starvation induces PUMA-mediated apoptosis, arachidonic acid-induced cell death is obviously detected in Serum-Free media condition (SF). Moreover, arachidonic acid can induce SF-induced apoptosis in Smad4-deficient cells, suggesting that arachidonic acid can work in Smad4- downstream pathway. Indeed, we can observe the selective suppression of PAK1-PUMA binding by AA treatment through GST-pull down assay. In addition, BSA can block the arachidonic acidinduced cell death like as Smad4-mediated apoptosis, whereas COX-2 inhibitor such as celecoxib shows a synergic effect in cancer cell death. Our results indicate that arachidonic acid is an important apoptosis trigger in human cancer cells. Together, these findings suggest that arachidonic acid could be a useful plausible target for cancer treatment.

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Cite the Article:

Ko S, Woo TG, Lee SH, Ha NC, Park BJ. Arachidonic Acid Induces Apoptosis Under Serum-Free Conditions by Blocking PAK1-Mediated PUMA Suppression. Clin Oncol. 2024;9:2053..