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J. He et al.
of which seems to be increasing the expression of cell cycle genes. p21 plays a crucial role in chidamide-induced G1 cell cycle arrest. HDAC1 regulates p21 expression to some extent. HDAC1 interacts with the p21 promoter by competing with the p53 protein to decrease the transcrip- tion of p21.21 Based on our results from MM cell lines, in chidamide-treated MM cells HDAC1 was released from
the p21 promotor, subsequently increasing p21 expression. Additionally, chidamide inhibited the expression of the Cyclin-D2 gene, thus inhibiting the functions of CDK4 and CDK6. Aberrant activation of the JAK2/STAT3 pathway is required for the pathogenesis of a variety of cancers.22,23 Inappropriate STAT3 activation protects cells from apopto- sis. HDAC3 targets STAT3, and inhibition of HDAC3
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Figure 6. Chidamide inhibited osteoclast differentiation in vitro. (A) Western blotting was used to detect the expression levels of key factors (DUSP1, c-fos, NFATc1, and HDAC10) during OC maturation; a-tubulin was used as the loading control. (B) Western blot analysis of the expression levels of pathway proteins including p- p38, p38, p-ERK, ERK, p-JNK, JNK p-AKT, and AKT; levels of key factors, including Cathepsin K, c-fos, NFATc1 and HDAC10, in OCs treated with different concentra- tions of chidamide. GAPDH was used as the loading control. Acetylation of H3K18 and H4K8 was also evaluated; H3 and H4 were used as loading controls. (C) TRAP staining of OCs treated with different concentrations of chidamide. F-actin ring formation. Rhodamine-conjugated phalloidin was used to visualize F-actin (red), and nuclei were stained with DAPI (blue), 200×. Pit formation assay of OCs treated with different concentrations of chidamide. (D) The number of TRAP-positive cells was reduced in cultures treated with increasing doses of chidamide, **P<0.01. (E) Calcium resorption was reduced in the presence of chidamide (0-1μM). Resorption in the lacunae area (%) diminished with increasing doses of chidamide, ***P<0.001. OC: osteoclasts; TRAP: tartrate-resistant acid phosphatase.
haematologica | 2018; 103(8)