Isobavachalcone exerts anti ‑proliferative and pro‑apoptotic effects on human liver cancer cells by targeting the ERKs/RSK2 signaling pathway.

Isobavachalcone exerts anti‑proliferative and pro‑apoptotic effects on human liver cancer cells by targeting the ERKs/RSK2 signaling pathway. Oncol Rep. 2019 Apr 02;: Authors: Li B, Xu N, Wan Z, Ma L, Li H, Cai W, Chen X, Huang Z, He Z Abstract Aberrant activation of the extracellular signal‑regulated kinases (ERKs)/ribosomal S6 kinase 2 (RSK2) signaling pathway is frequently determined in various human tumor types, including liver cancer, and has been considered as a promising target for cancer chemoprevention and therapy. In the present study, using computer‑aided virtual screening and molecular docking, isobavachalcone (IBC), a natural chalcone compound, was identified to be an ATP‑competitive inhibitor targeting ERK1/2 and RSK2. Cell Counting Kit‑8, EdU incorporation and colony formation assays were used to detect the effects of IBC on cell viability and proliferation, and the results demonstrated that IBC effectively inhibited the proliferation of liver cancer HepG2 and Hep3B cells, whereas it had no notable cytotoxic effect on immortal liver L02 cells. Flow cytometric analysis and western blotting further revealed that IBC caused significant levels of apoptosis on liver cancer cells via the caspase‑dependent mitochondria pathway. The computer prediction was confirmed with pull‑down and in vitro kinase assays, in which IBC directly bound with ERK1/2 and RSK2, and dose‑dependently blocked RSK2 kinase activity ...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research