SAHA/TRAIL combination induces detachment and anoikis of MDA-MB231 and MCF-7 breast cancer cells

摘要: Abstract SAHA, an inhibitor of histone deacetylase activity, has been shown to sensitize tumor cells apoptosis induced by TRAIL, a member TNF-family. In this paper we investigated the effect SAHA/TRAIL combination in two breast cancer cell lines, ERα−positive MCF-7 and ERα−negative MDA-MB231. Treatment MDA-MB231 with SAHA TRAIL caused detachment followed anoikis, form which occurs after detachment, while treatment or alone did not produce these effects. The effects were more evident cells, chosen for ascertaining mechanism action. Our results show that decreased level c-FLIP, thus favouring interaction specific death receptors DR4 DR5 consequent activation caspase-8. These increased when treated combination. Because z-IEDT-fmk, caspase-8, prevented both cleavage focal adhesion-kinase FAK suggest caspase-8 can be responsible decrement detachment. addition, dissipation ΔΨm, caspase-3 phospho-EGFR phospho-ERK1/2, kinase is involved phosphorylation BimEL. Therefore, co-treatment also phospho-BimEL concomitant increase dephosphorylated BimEL, plays important role induction anoikis. findings potential application clinical trials cancer.