(404) Http failure response for https://api.library.tamu.edu/scholars-discovery/directoryViews: 404 Not Found
Activation of caspase-3 activity and apoptosis in MDA-MB-468 cells by N(omega)-hydroxy-L-arginine, an inhibitor of arginase, is not solely dependent on reduction in intracellular polyamines. | Academic Article individual record

We have shown previously that (NOHA) an intermediate in the nitric oxide (NO) synthetic pathway and an inhibitor of arginase significantly reduced intracellular polyamines, activated caspase-3 and induced apoptosis in the human breast cancer cell line MDA-MB-468. These actions of NOHA were abolished in the presence of exogenous L-ornithine suggesting that a reduction in the intracellular polyamine content might be responsible for the activation of caspase-3 and apoptotic actions of NOHA. In order to further explore this possibility, we used SAM-486A and alpha-difluoromethylornithine (DFMO), which are inhibitors of S-adenosylmethionine decarboxylase (SAMDC), and ornithine decarboxylase (ODC), respectively, either alone or in combination to reduce the intracellular polyamine levels. We then assessed whether a reduction in polyamine levels by these two compounds to a similar degree to that produced by NOHA activated caspase-3 which occurs prior to the onset of apoptosis. We observed that both SAM-486A and DFMO, either alone or in combination, inhibited cell proliferation, induced p21 and arrested cells in the G(0)-G(1) phase of the cell cycle but failed to activate caspase-3 as assessed by enzymatic assay of caspase-3, western blot analysis of the proteolytic cleavage of caspase-3 protein as well as TUNEL assay. Furthermore, pre-incubation of the cells with SAM-486A and DFMO for 4 days, either alone or in combination significantly inhibited the activation of caspase-3 and apoptosis by NOHA when compared with that observed with cells treated with NOHA alone. Our results, therefore, indicate that the activation of caspase-3 and apoptosis observed with NOHA cannot be solely explained by a reduction in intracellular polyamine levels and that other mechanisms need to be also considered.

author list (cited authors)
Singh, R., Pervin, S., Wu, G., & Chaudhuri, G.
publication date
published in
  • Cyclins
  • Arginase
  • Cell Division
  • Ornithine
  • Tumor Cells, Cultured
  • Adenosylmethionine Decarboxylase
  • Enzyme Inhibitors
  • Apoptosis
  • Cyclin-Dependent Kinase Inhibitor P21
  • Breast Neoplasms
  • Polyamines
  • Caspases
  • In Situ Nick-End Labeling
  • Ornithine Decarboxylase
  • Caspase 3
  • Reverse Transcriptase Polymerase Chain Reaction
  • Enzyme Activation
  • Blotting, Western
  • Arginine
  • Humans