The Antiproliferative Effect of EPA in HL60 Cells is Mediated by Alterations in Calcium Homeostasis

• DOI: 10.1007/s11745-008-3263-5
• Publication Date: 2008-11-19T15:57:29Z
• Authors: Jens Erik Slagsvold; Caroline Hild Hak...; Turid Follestad; Hans Einar Krokan; Svanhild Arentz S...
• Keywords: HL60

Studies show that n-3 polyunsaturated fatty acids (PUFA) inhibit proliferation and induce apoptosis in cancer cells. Recent reports indicate this effect is due to activation of the unfolded protein response (UPR). However, what causes has been unclear. We examined effects eicosapentaenoic acid (EPA) on human leukemia cell line HL60 econazole (Ec) resistant clone E2R2. Ec depletes Ca(2+) from ER blocks influx mammalian cells, leading UPR apoptosis. EPA inhibited growth cells strongly, while E2R2 were much less affected. Gene expression analysis revealed extensive changes transcripts related homeostasis, Ca(2+)-homeostasis cycle/apoptosis. Protein levels phosphorylated eIF2alpha, a selective translation inhibitor hallmark, activating transcription factor 4 (ATF4) sequestosome-1 moderately increased, whereas cycle/progression cyclin D1 was decreased HL60. In contrast, concentrations strongly caused had no level these markers Given only known difference between Ec-resistance, our results suggest inhibitory initially meditated through alterations followed by UPR.