Scriptaid inhibits cell survival, cell cycle, and promotes apoptosis in multiple myeloma via epigenetic regulation of p21

•The histone deacetylase (HDAC) inhibitor Scriptaid inhibits multiple myeloma (MM) cell proliferation and cycle.•Scriptaid induces MM cell apoptosis.•p21 is the key regulator of Scriptaid-mediated cell death.•Scriptaid activates p21 transcription by increasing the H3Ac level at its promoter. Multiple myeloma (MM) is an extremely serious plasma cell malignancy. Despite the recent introduction of chemotherapies such as bortezomib and lenalidomide, it remains an incurable disease due to the high rate of relapse and the development of drug resistance. Epigenetic regulation is closely related to MM progression, but the epigenetic modification mechanism of MM cell apoptosis has remained unclear. As a novel histone deacetylase inhibitor (HDACi), Scriptaid's possible roles in MM progression have not been explored. Herein, we found that Scriptaid decreased several human MM cell viabilities in a dose-dependent manner. Scriptaid was also able to dose dependently and significantly induce MM cell cycle arrest at the G2/M phase. Moreover, Scriptaid facilitates p21 transcriptional activities by mediating H3Ac gene-activated modification, eventually leading to MM cell apoptosis. Overall, our results show that Scriptaid is an inducer of MM cell death, suggesting the possibility for Scriptaid-mediated therapeutics to cure refractory/relapsed MM.