Modulation of cellular proliferation and induction of apoptosis in a human lymphoma cell line after treatment with selective lipoxygenase inhibitors.

Abstract

It has long been recognized that eicosanoids have the ability to modulate cellular proliferation in many in vitro cell culture systems. It had also been recognized that both lipoxygenase and cyclooxygenase inhibitors have the ability to alter cellular proliferation in many cell types. Previously, we have shown that lipoxygenase inhibition is associated with decreased cellular proliferation in human lymphoma (1), leukemic blast- crisis cells (2), prostate adenocarcinoma (3), glioblastoma (4), and squamous cell carcinoma cells (5). In some cases, subpopulations of treated cells appear to undergo changes associated with cellullar differentiation (6,7). Classic inhibitors of eicosanoid metabolism have been shown to have multiple physiologic effects, many of which are not attributable to their inhibition of eicosanoid synthesis (8, 9). In the present work, U937 cells were cultured with selective 5- lipoxygenase inhibitors as well as the less selective inhibitors, nordihydroguaeretic acid (NDGA) and eicosatetraynoic acid (ETYA), and examined for effects on cell proliferation and the induction of programmed cell death.