In Vitro Effects of Selective COX and LOX Inhibitors and Their Combinations with Antineoplastic Drugs in the Mouse Melanoma Cell Line B16F10

The constitutive expression or overactivation of cyclooxygenase (COX) and lipoxygenase (LOX) enzymes results in aberrant metabolism arachidonic acid poor prognosis melanoma. Our aim is to compare the vitro effects selective COX-1 (acetylsalicylic acid), COX-2 (meloxicam), 5-LOX (MK-886 AA-861), 12-LOX (baicalein) 15-LOX (PD-146176) inhibition terms proliferation (SRB assay), mitochondrial viability (MTT caspase 3-7 activity (chemiluminescent 2D antimigratory (scratch assay) synthesis eicosanoids (EIA) B16F10 cell line (single treatments). We also explore their combinatorial pharmacological space with dacarbazine temozolomide (median effect method). Overall, our single treatments show a superior cytotoxic efficacy LOX inhibitors over COX against cells. PD-146176 caused strongest antiproliferation which was accompanied by cycle arrest G1 phase an >50-fold increase caspases 3/7 activity. When selected are combined antineoplastic drugs, only meloxicam provides clear synergy, mostly antagonizing. These apparent contradictions between combination treatments, together some paradoxical observed biosynthesis after FLAP short term incubations, warrant further mechanistical vivo scrutiny.