DNMT and HDAC Inhibition Block the Rise of Tumor Growth in Cancer Stem-like Cells

A study published in 2015 found that breast cancer stem cells are intrinsically sensitive to both genetic and epigenetic modifications and are therefore susceptible to epigenetic based therapies. Combined inhibition of DNA methyltransferase (DNMT) and histone deacetylase (HDAC) may prove a potent route to prevent tumorigenicity in this and other cancer models.

In this study, the DNMT inhibitor 5-azacytidine and the HDAC inhibitor butyrate  reduced the abundance of cancer stem cells while increasing the overall survival rate in a mouse model. Further analysis indicated that the 5-azacytidine plus butyrate therapy blocked growth-promoting signaling molecules such as RAD51AP1 and SPC25 through the inhibition of chromatin modifiers. These signaling molecules are important in DNA damage repair and kinetochore assembly, and are significantly over expressed in human breast tumor tissues.

Epigenetic modifiers are a promising group of compounds that have seen a large rise in research focus over the past decade. LKT Labs carries a number of DNMT and HDAC  inhibitors, in addition to other epigenetic modifiers. A  small selection of these popular small molecules are below:

A9602 Azacitidine

E5477 Entinostat

M3476 Mithramycin

T6933 Trichostatin A

V5734 Vorinostat

Pathania R, Ramachandran S, et al., Combined inhibition of DNMT and HDAC blocks the tumorigenicity of cancer stem-like cells and attenuates mammary tumor growth. Cancer Res. 2016 April.