Trichostatin A (TSA) was originally isolated as an antifungal antibiotic along with its fermentation congeners trichostatin B ((TSA)3-Fe) and the D-glucopyranosides trichostatin C and D. TSA inhibits HDAC in the low nanomolar range and is an inducer of histone hyperacetylation, both in vitro and in vivo. It inhibits all class I and II deacetylases to a similar extent in both tumor and non-tumor cells, although HDAC4 is slightly resistant when compared with HDAC1 and HDAC6. Class III HDAC is not affected by TSA. It has been shown that TSA dosedependently inhibits growth and induces apoptosis in a plethora of carcinoma cell lines in vitro. Recently, it was also found that TSA inhibits angiogenesis, which is important for the growth and metastasis of solid tumors, both in vivo and in vitro. In HT-29 colon carcinoma cells, a single dose of TSA induced transient hyperacetylation of histone H4 resulting in the induction of p21WAF1/Cip1 and inhibition of cellular proliferation at both the G1 and G2 phases of the cell cycle. Growth inhibition was associated with decreased cyclin D1 mRNA and cdk6 protein levels and increased cyclin D3 protein and p21WAF1/Cip1 mRNA levels. Cyclin D1 protein, cyclin D3 mRNA, cdk2 and cdk4 remained unaffected. In addition, TSA induced apoptosis by upregulating the expression of the pro-apoptotic genes ID1, ID2 and ID3, whereas the expression of the anti-apoptotic genes BclxL and Hsp27 was decreased In vivo, TSA induces differentiation and shows chemotherapeutic activity against N-methylnitrosureainduced rat mammary cancer without toxic side effects. TSA may also have therapeutic potential for the treatment of a variety of genetic and infectious diseases since silenced, transduced genes are reactivated probably due to structural changes of the chromatin on integrated viral sequences.

Cycloheximide is an antibiotic produced by fermentation culture of Streptomyces griseus, Streptomyces noursei, Streptomyces albulus, Streptomyces naraensis, or other cycloheximide-producing microorganism. It was first discovered by A. Whiffen et al. in 1946. She observed the activity of the compound against the yeasts and it became known as the first antifungal antibiotic. Cycloheximide has been marketed as a plant fungicide for many years and this use continues mainly against fungal diseases of turf and for powdery mildew on roses. More recently, cycloheximide has been recognized and is being developed as an abscission agent for citrus fruits and olives. Due to significant toxic side effects, including DNA damage, teratogenesis, and other reproductive effects, cycloheximide is generally used only in in vitro research applications, and is not suitable for human use as a therapeutic compound. Cycloheximide is an antimitotic and an inhibitor of the synthesis of both DNA and protein.

L-erythro-Sphingosine (also known as erythro-Sphingosine, (+)) – is an inactive isomer from the four possible stereoisomers of sphingosine. This isomer can induce dephosphorylation of pRb protein with EC50 = 5 μM. -erythro-Sphingosine is a weak substrate of ceramidase and has shown competitive inhibition properties.