%0 Journal Article
%T SIRT1 and AROS suppress doxorubicin-induced apoptosis via inhibition of GSK3¦Â activity in neuroblastoma cells
%A Eun-Joo Kim
%A Jeong Woo Kim
%A Ji Hye Yang
%J Animal Cells and Systems
%D 2020
%R https://doi.org/10.1080/19768354.2020.1726461
%X ABSTRACT SIRT1, the best-characterized member of the sirtuin family of deacetylases, is involved in cancer, apoptosis, inflammation, and metabolism. Active regulator of SIRT1 (AROS) was the first identified direct regulator of SIRT1. An increasing number of reports have indicated that SIRT1 plays an important role in controlling brain tumors. Here, we demonstrated that depletion of SIRT1 and AROS increases doxorubicin-mediated apoptosis in human neuroblastoma SH-SY5Y cells. Glycogen synthase kinase 3¦Â (GSK3¦Â) promoted doxorubicin-mediated apoptosis, but this effect was abolished by overexpression of SIRT1 and AROS. Interestingly, SIRT1 and AROS interacted with GSK3¦Â and increased inhibitory phosphorylation of GSK3¦Â on Ser9. Finally, we determined that AROS cooperates with SIRT1 to suppress GSK3¦Â acetylation. Taken together, our results suggest that SIRT1 and AROS inhibit GSK3¦Â activity and provide additional insight into drug resistance in the treatment of neuroblastoma
%U https://www.tandfonline.com/doi/full/10.1080/19768354.2020.1726461