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 IC(50) 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.