Table 3.
Role of HDACis in Cancer
| pathway | genes/signalings | tumours affected | representative drug |
|---|---|---|---|
| apoptosis | mutant p53 ↓ [96, 97] | TNBC and pancreatic cancer | SAHA, NaB , VPA and TSA |
|
proapoptotic proteins of Bcl-2 family, such as Bim, Bmf, Bax, Bak and Bik ↑ antiapoptotic proteins of Bcl-2 family, such as Bcl-2, Bcl-XL, Bcl-w and Mcl-1 ↓ [93] |
melanoma | SBHA | |
| XIAP ↓ [98, 99] | Mesothelioma and leukemia | LBH589 and LAQ824 | |
| TBP2 ↑-Trx ↓-ASK1 signaling ↑ [100] | prostate cancer | SAHA | |
| ROS ↑ [101] | CLL | MS-275 | |
|
TRAIL-DR5 ↑ FASL-FAS (Apo-1 or CD95) ↑ |
leukaemia, breast cancer | VPA, SAHA and TSA | |
| human RAD23 homolog B (HR23B) ↑ [104] | U2OS cells | SAHA | |
| erbB2 (Her-2) ↓ [105, 106] | breast cancer | TSA and LAQ824 | |
| cell death |
NF-κβ ↑ [107] AKT-mTOR signaling ↓ [94] |
Prostate Cancer glioblastoma |
SAHA SAHA |
| cell arrest | CDKN1A (encoding p21 WAF1/CIP1)↑ [108–110] | CML-BC cells, colon cancer and bladder carcinoma | LAQ824, SAHA and Butyrate |
| p27 ↑ [111] | leukemia and breast cancer | SAHA and TSA | |
| GADD45 α and GADD45 β ↑ [112] | colon carcinoma | TSA and Butyrate | |
| TGF-βRII ↑ - c-MYC ↓ [113] | Ewing's sarcoma (EWS) and neuroblastoma | MS-275 | |
| angiogenesis |
HIF-1a ↓ [114] VEGF ↓ [115] |
Lewis lung carcinoma HepG2 cell |
FK228 TSA |
| DNA repair |
Ku86 ↓ Ku70 ↓ [116] |
melanoma cells | sodium butyrate (NaB) |
|
RAD51 ↓ BRCA1&2 ↓ [117] |
human squamous carcinoma cells (SQ-20B) | TSA | |
| immunity |
MHC class I genes ↑ tumor antigens ↑ PD-1 ligands ↑ [118] |
melanoma | LBH589, MS-275 and MGCD0103 |
| Treg cells ↓ [119] | renal and prostate cancer | entinostat |
‘↑’ or ‘↓’, represent the up-regulated or down-regulated trend of gene expression, respectively.