Rapid decrease of intracellular pH associated with inhibition of Na+/H+ exchanger precedes apoptotic events in the MNK45 and MNK74 gastric cancer cell lines treated with 2-aminophenoxazine-3-one.

摘要: The effects of Phx-3 on changes in intracellular pH (pHi) the MKN45 and MKN74 human gastric cancer cell lines were evaluated order to determine mechanism for proapoptotic 2-aminophenoxazine-3-one (Phx-3) these cells. (100 μM) reduced pHi from 7.45 5.8, 7.5 6.2 within 1 min engagement with Such a decrease was closely correlated dose this phenoxazine continued 4 h. activity Na+/H+ exchanger isoform l (NHE1), which is involved H+ extrusion cells, dose-dependently suppressed by greatly presence 100 μM Phx-3. This result indicates that cells associated inhibition NHE1 morphology at 24 h after treatment indicated shrinkage condensation nuclear chromatin structure, are characteristic apoptotic events Cytotoxicity against extensive because almost all lost viability 20 Phx-3, nearly 50% 50 These results suggest rapid caused might disturb homeostasis, leading cytotoxic good candidate therapeutics intractable conventional chemopreventive therapies.