Table 1.

Histone deacetylase-associated mechanisms of action in carcinogenesis

Increased expression of genes associated with the cell cycle, increasing proliferation, by overpassing the G1-S checkpoint, either by increasing CDK-2 and -4[12], or by inhibiting p21 protein that arrests cell cycle[13].

Inhibition of both the intrinsic and extrinsic apoptotic pathways[15].

Acyl group removal from other non-histone proteins, like transcription factors and regulatory proteins, indirectly affecting cellular proliferation[8].

Increased macropinocytosis, a process closely related to cellular migration and increased metastatic potential[19].

Increased chemotherapy resistance in tumor cells[21].

Protection from cellular damage caused by ROS[22].

Inhibition of angiogenesis by decreasing VEGF and HIF-1α[22].

Reduction of E-cadherin and increased vimentin expression, increasing metastatic potential[12].

Increased HSP function, conferring stability to oncogenic proteins[33].

Decreased function of DNA repair enzymes[39].

CDK: Cyclin dependent kinases; ROS: Reactive oxygen species; VEGF: Vascular endothelial growth factor; HIF-1α: Hypoxia inducible factor 1-alpha; HSP: Heat-shock proteins.