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

Abstract

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.

Activation of the Nuclear Factor-kappa B Signaling Pathway Damages the Epithelial Barrier in the Human Pancreatic Ductal Adenocarcinoma Cell Line HPAF-II

“…Other researchers found that inhibiting the activation of NF-κB restrained the increased permeability of epithelial cells induced by TNF-α. 18 In this study, activated NF-κB did not upregulate the permeability of monolayers but inhibited NF-κB downregulated the permeability, suggesting that the activity of the NF-κB signaling pathway is closely related to the permeability of pancreatic duct epithelial cells and the epithelial barrier.…”

“…Since phosphorylation is necessary for the transcriptional activity of p65, p-p65 is more important to indicate the activation of NF-κB. 18 The results above indicated that TNF-α activated the expression and phosphorylation of p65. On the other hand, in the cells treated with PDTC for 1.5 hours, p65 mRNA expression detected by qPCR was downregulated compared with the TNF-α group (Fig.…”

Salt-Tolerant Plants, Halophytes, as Renewable Natural Resources for Cancer Prevention and Treatment: Roles of Phenolics and Flavonoids in Immunomodulation and Suppression of Oxidative Stress towards Cancer Management

“…Bigelovii A inhibited the growth of HL-60, MCF-7, and HepG2 cell lines, with IC 50 values of 6.18, 78.08, and 13.64 μM, respectively. Bigelovii A also exhibited strong cytotoxic effects against several breast cancer cell lines (MCF-7, MDA-MB-231, and MDA-MB-468), and induced apoptosis by downregulating the NF-kB signaling genes Cyclin D1 and COX-2 [ 203 ]. Known compounds of 30-nortriterpenoid and oleanane-type triterpenoid glycosides were also isolated from Salicornia bigelovii , but only the 3- O -β- D -glucuropyranosyl-30-norolean-12,20-(29)-dien-28-oic-acid-28- O -β-d-glucopyranoside was cytotoxic-active against HL-60 cell lines, with an IC 50 value of 31.87 μM [ 202 ].…”

Mitochondrial dysfunction in heart diseases: Potential therapeutic effects of Panax ginseng

“…Zhang et al demonstrated that Rb1 has a protective effect on DCM by inhibiting caspase family proteins and NF⁃κB pathway ( Zhang et al, 2021 ), which is similar to the protective effect of Rb1 on MI/R ( Figure 3C ; Fan et al, 2020 ; Yan et al, 2014 ). NF⁃κB is a key factor in triggering inflammatory response and regulating apoptotic response, and its phosphorylation and acetylation are indicative of mitochondria-dependent apoptotic signals ( Guan et al, 2018 ). The expression level of silent information regulator 1 (Sirt1) increased significantly after Rb1 stimulation, suggesting that it can activate Sirt1 ( Zhang et al, 2021 ).…”