The potential anticancer activities of histone deacetylase (HDAC) inhibitors and 
DNA methyltransferase (DNMT) inhibitors have been extensively studied in recent 
years. HDAC inhibitors suppress the activities of multiple HDACs, leading to an 
increase in histone acetylation. This histone acetylation induces an enhancement 
of the expression of specific genes that elicit extensive cellular morphologic 
and metabolic changes, such as growth arrest, differentiation and apoptosis. 
DNMT inhibitors, such as 5-aza-cytidine (5-aza-CR) and 5-aza-2'-deoxycytidine 
(5-aza-CdR) are also widely studied because DNA hypomethylation induces the 
re-activation of tumor suppressor genes that are silenced by 
methylation-mediated mechanisms. Recently, the combination of HDAC inhibitors or 
demethylating agents with other chemo-therapeutics has gained increasing 
interest as a possible molecularly targeted therapeutic strategy. In particular, 
the combination of HDAC inhibitors with demethylating agents has become 
attractive since histones are connected to DNA by both physical and functional 
interactions. To date, the accumulating evidence has confirmed the hypothesis 
that the combination of HDAC and DNMT inhibition is very effective (and 
synergistic) in inducing apoptosis, differentiation and/or cell growth arrest in 
human lung, breast, thoracic, leukemia and colon cancer cell lines. This review 
will discuss the in vitro effects of HDAC inhibitors, such as trichostatin A 
(TSA), sodium butyrate, depsipeptide (FR901228, FK228), valproic acid (VPA) and 
suberoylanilide hydroxamic acid (SAHA), and the demethylating agent, 5-aza-CdR 
used alone and in combination treatment of human cancer cells and the possible 
mechanisms involved.