The synergistic effect of SAHA and parthenolide in MDA-MB231 breast cancer cells.

摘要: The sesquiterpene lactone Parthenolide (PN) exerted a cytotoxic effect on MDA-MB231 cells, triple-negative breast cancer (TNBC) cell line, but its effectiveness was scarce when employed at low doses. This represents an obstacle for therapeutic utilization of PN. In order to overcome this difficulty we associated PN the suberoylanilide hydroxamic acid (SAHA), histone deacetylase inhibitor. Our results show that SAHA synergistically sensitized cells It is noteworthy treatment with alone stimulated survival pathway Akt/mTOR and consequent nuclear translocation Nrf2, while induced autophagic activity. However, were treated SAHA/PN combination, suppressed Akt/mTOR/Nrf2 pathway, reduced prosurvival activity SAHA. addition combination GSH depletion, fall in Δψm, release cytochrome c, activation caspase 3 apoptosis. Finally demonstrated combined maintained both hyperacetylation histones H3 H4 by down-regulation DNMT1 expression Inhibition DNA-binding NF-kB, which determined PN, also observed after treatment. conclusion, inhibits cytoprotective responses single compounds, does not alter mechanisms leading effects. Taken together our suggest could be candidate TNBC therapy.