Superior anti-DLBCL efficacy of novel organic arsenical Z2-A-Z2 through ROS-mediated apoptosis and critical NF-κB/IκBα signaling pathway inhibition - PubMed
3 hours ago
- #DLBCL treatment
- #organic arsenical
- #NF-κB inhibition
- A novel organic arsenical compound, Z2-A-Z2, was synthesized and evaluated for its efficacy against diffuse large B-cell lymphoma (DLBCL).
- Z2-A-Z2 showed potent and selective anti-proliferative activity against DLBCL cell lines, with an average IC₅₀ of approximately 1.1 µM, which is 3- to 6-fold superior to arsenic trioxide (ATO).
- The compound induced mitochondrial-mediated apoptosis and G2/M cell cycle arrest through dual action: triggering oxidative stress (ROS) and inhibiting the NF-κB/IκBα signaling pathway.
- ROS was found to act upstream to suppress p65 activity, while p65 modulates drug-induced ROS generation, indicating bidirectional regulation.
- In vivo studies using xenograft models confirmed robust tumor growth suppression, reduced NF-κB/IκBα activity, increased apoptosis, and an excellent safety profile.