Low dose Emodin induces tumor senescence for boosting breast cancer chemotherapy via silencing NRARP.
Biochem Biophys Res Commun. 2018 Nov 10 ;505(4):973-978. Epub 2018 Sep 28. PMID: 30274778
PURPOSE: The resistance to 5-FU often limits its clinical effectiveness on breast cancer treatment. Combination therapy thus is employed to overcome this treatment resistance. We here report a potent antitumor effect of Emodin at low dose on chemotherapy sensitivity of MCF-7 breast cancer cells.
METHODS: Cell viability, apoptosis, glutathiones (GSH) concentration and Reactive oxygen species (ROS) activity following Emodin and 5-FU treatment was assessed. Cellular senescence following combined treatment and silence of NRARP was examined by senescence-associatedβ-galactosidase analysis. Western blot analysis was used to determine changes in the expression of p21, p16, p27, E2F1 and NRARP.
RESULTS: Low dose Emodin potentiates 5-FU-induced apoptosis of breast cancer cells, in association with inhibition of NRARP, resulting in cellular senescence. RNA interference of NRARP induced cellular senescence in MCF-7 breast cancer cells. Furthermore, the cellular senescence induced by Emodin and 5-FU treatment could be reverted by pcDNA-NRARP.
CONCLUSION: These findings provide preclinical evidence for repurposing use of Emodin in combination with chemotherapeutic agents to treat breast cancer as an alternative salvage regimen.