Protein tyrosine phosphatase alpha regulates cell detachment and cell death profiles induced by nitric oxide donors in the A431 human carcinoma cell line

摘要

We investigated the role of protein tyrosine phosphatase-alpha (PTPα) expression in the cell death profile of thenA431 human carcinoma cell line that was induced by cytotoxic concentrations of the nitric oxide (NO) donorsnsodium nitroprusside (SNP) and 3,3-bis-(aminoethyl)-1-hydroxy-2-oxo-1-triazene (NOC-18). Both NO donorsnpromoted extensive cell detachment in A431 parental cells as compared to the detachment observed fornA431 cells that ectopically expressed PTPα (A431 (A27BPTPαn) cells). The NO-induced cell deathncharacteristics for both cell lines were examined. After incubation for 10 hours with 2.0 mM SNP, attached orndetached A431 cells underwent apoptosis. Cells were highly positive for Annexin-V, featured increasedncleavage of procaspase-8, activation of downstream caspase-3, and activation of poly-ADP-ribosenpolymerase 1 (PARP-1). In contrast, exposure of A431 (A27BPTPαn) cells to 2.0 mM SNP produced annincrease in the release of lactate dehydrogenase and enhanced incorporation of propidium iodide. Innaddition, A431 (A27BPTPαn) cells showed partial inhibition of the activities of caspase-8, caspase-3, andnPARP-1 upon detachment and cell death induced by SNP treatment. Results indicate that necrotic cellndamage was induced, characterized by cellular swelling and lysis. We conclude from these results that PTPαnregulates the A431 tumor cell death profile mediated by NO donors. Expression of PTPα or its absence mayndetermine the occurrence of NO-induced cell death with necrotic or apoptotic features, respectively.