Background:

SBHA (suberohydroxamic acid) is a Histone deacetylase (HDAC) inhibitor, ID50 for HDAC1 and HDAC3 are 0.25 and 0.3 μM, respectively.

HDAC is an enzyme that deacetylates lysine residues on the N-terminal of the core histones. It is required for transcriptional modulation, cell cycle regulation and development.

In MEL cells, SBHA leads to the accumulation of acetylated H4, indicating the hydroxamic acid groups are involved in increasing potency and inhibition of HDAC activity. In Jurkat cells, SHBA inhibits the HDAC1 and HDAC3 activities with IC50 value of 0.25 and 0.3 μm respectively. [1]

In melanoma cell lines, SBHA also induces apoptosis and mitochondrial membrane permeability in a caspase-dependent manner. SBHA down-regulates main antiapoptotic proteins such as Bcl-XL and Mcl-1 and up-regulates proapoptic proteins such as Bim, Bax and Bak. In addition, SBHA induces translocation of Bim to mitochordria and its association with Bcl-2. [2]

参考文献:
1.  Richon VM, Emiliani S, Verdin E et al. A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases. Proc Natl Acad Sci U S A. 1998 Mar 17; 95(6):3003-7.
2.  Zhang XD, Gillespie SK, Borrow JM, Hersey P. The histone deacetylase inhibitor suberic bishydroxamate regulates the expression of multiple apoptotic mediators and induces mitochondria-dependent apoptosis of melanoma cells. Mol Cancer Ther. 2004 Apr; 3(4):425-35.