Induction of apoptosis by Bigelovii A through inhibition of NF‑κB activity.

Bigelovii A is a 30‑nortriterpenoid glycoside, isolated from Salicornia bigelovii Torr. Until now, the effect of Bigelovii A on breast cancer treatment was unknown. The present research indicated that Bigelovii A significantly inhibited the proliferation of human breast cancer cells (MCF‑7, MDA‑MB‑231 and MDA‑MB‑468) in a concentration‑dependent manner. It was particularly effective in MCF7 cells, with an IC50 value of 4.10±1.19 µM. The anti‑proliferative effect of Bigelovii A was ascribed to the induction of apoptosis, which was characterized by chromatin condensation, externalization of phosphatidylserine on the plasma membrane, hypodiploid DNA, activation of caspases and poly (ADP‑ribose) polymerase cleavage. Furthermore, Bigelovii A reduced B-cell lymphoma 2 (Bcl‑2) and B‑cell lymphoma‑extra large (Bcl‑xl) expression and caused disruption of mitochondrial membrane potential, which are indicative features of mitochondria‑dependent apoptotic signals. It was also identified that Bigelovii A downregulated the constitutive activation of nuclear factor (NF)‑κB, as indicated by the electrophoretic mobility gel shift assay and immunocytochemistry. Furthermore, Bigelovii A suppressed constitutive IκBα phosphorylation via inhibition of IκB kinase activity. In addition to the effects on Bcl‑2 and Bcl‑xl, Bigelovii A also downregulated the expression of the NF‑κB‑regulated gene products, Cyclin D1 and cyclooxygenase‑2. This led to the induction of apoptosis and arrest of cells at the G1 phase of the cell cycle.