体外研究 (In Vitro) | Droxinostat selectively inhibits HDAC3, HDAC6, and HDAC8 with IC50values of 16.9 μM, 2.47 μM, and 1.46 μM, respectively[1]. Droxinostat (0, 10, 20, or 40 μM; 48 h) suppresses HDAC3 expression and induces acetylation of histones H3 and H4[2]. Droxinostat (0, 10, 20, 40, and 80 μM; 0, 24, 48, 72, 96, and 120 h) inhibits cell proliferation and colony formation in HepG2 and SMMC-7721 cells[2]. Droxinostat (0 to 80 μM; 48 h) induces hepatoma cell apoptosis by activating mitochondrial apoptotic pathways and downregulating FLIP[2].
Western Blot Analysis[2] Cell Line: | SMMC-7721 and HepG2 (Human liver carcinoma cell lines) | Concentration: | 0, 10, 20, or 40 μM | Incubation Time: | 48 h | Result: | Significantly decreased the expression of HDAC3 with dose-dependent in HepG2 and SMMC-7721 cell lines. Significantly enhanced the expression of acetyl-H3 (Ac-H3) and acetylH4 (Ac-H4) in HepG2 and SMMC-7721 cells in a dose-dependent manner. Upregulated the levels of phospho-p53 and cleaved caspase 3 protein and downregulated the levels of Bcl-2. Markedly increased the Bax/Bcl-2 ratio in a dose-dependent manner and increased the expression of cleaved PARP protein in HepG2 cells in a dose-dependent manner. Significant reduced the FLIP expression and enhanced caspase 8 activity in both HepG2 and SMMC-7721cell. |
Cell Proliferation Assay[2] Cell Line: | SMMC-7721 and HepG2 | Concentration: | 0, 10, 20, 40, and 80 μM | Incubation Time: | 0, 24, 48, 72, 96, and 120 h | Result: | Decreased the viability with a time-and dose-dependent in both cell lines. |
Apoptosis Analysis[2] Cell Line: | SMMC-7721 and HepG2 | Concentration: | 0 to 80 μM | Incubation Time: | 48 h | Result: | Clearly led to dose-dependent apoptosis, but did not induce hepatoma cell apoptosis at 10 μM and had an apoptotic effect at a starting concentration of 20 μM. |
RT-PCR[2] Cell Line: | SMMC-7721 and HepG2 | Concentration: | 20 μM and 40 μM | Incubation Time: | 48 h | Result: | Significantly increased the mRNA levels of Bax and p53 genes associated with the mitochondrial p53 apoptosis pathway in a dose-dependent manner in HepG2 and SMMC-7721 cells. Significantly increased the Bcl-2 mRNA levels in SMMC-7721 cells at a concentration of 40 uM and also increased the Bax/Bcl-2 mRNA ratio. |
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