Berbamine Suppresses the Growth of Gastric Cancer Cells by Inactivating the BRD4/c-MYC Signaling Pathway.

PURPOSE: Berbamine (Ber), a bioactive constituent extracted from a traditional Chinese medicinal herb, has been shown to exhibit broad inhibitory activity on a panel of cancer cell types. However, its effects and the underlying molecular mechanisms on gastric cancer (GC) remain poorly understood. METHODS: The anti-growth activity of Ber on two GC cell lines and normal gastric epithelial cell line were evaluated using MTS and clone formation assay. Flow cytometry analysis was employed to evaluate the cell cycle distribution and apoptosis of GC cells. Western blot and quantitative PCR (qPCR) analysis were employed to investigate the anti-GC mechanism of Ber. The inhibitory activity and binding affinity of Ber against BRD4 were evaluated by homogeneous time-resolved fluorescence (HTRF) and surface plasmon resonance (SPR) assay, respectively. Molecular docking and molecular simulations were conducted to predict the interaction mode between BRD4 and Ber. RESULTS: The results demonstrated that Ber reduced the proliferation of GC cell lines SGC-7901 and BGC-823 and induced cell cycle arrest and apoptosis. Mechanistically, Ber was identified as a novel natural-derived BRD4 inhibitor through multiple experimental assay, and its anti-GC activity was probably mediated by BRD4 inhibition. Molecular modeling studies suggested that Ber might bind to BRD4 primarily through hydrophobic interactions. CONCLUSION: Our study uncovered the underlying anti-GC activity of Ber in vitro and suggested that Ber holds promise as a potential lead compound in the discovery of novel BRD4 inhibitors.

Resveratrol suppresses the invasion and migration of human gastric cancer cells via inhibition of MALAT1-mediated epithelial-to-mesenchymal transition.

Resveratrol, a natural polyphenolic phytoalexin, was reported to exert multiple anticancer effects as a traditional Chinese medicine. However, research regarding the anticancer mechanism of resveratrol for the treatment and prevention of gastric cancer has reported conflicting results. In the present study, it was determined that resveratrol inhibited cell viability in a dose-dependent manner in the human gastric cancer cell line BGC823. Cell migration and invasion were suppressed significantly following treatment with 200 µM resveratrol. Additionally, resveratrol inhibited metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression, which was overexpressed in gastric cancer cells. Further experiments revealed that MALAT1 knockdown suppressed cell viability, migration, invasion and epithelial-to-mesenchymal transition in BGC823 cells. The present study indicated that resveratrol inhibited migration and invasion in human gastric cancer cells via suppressing MALAT1-mediated epithelial-to-mesenchymal transition, providing novel evidence for understanding the anticancer mechanism of resveratrol.