Butyrate-induced differentiation in leukemic myeloid cells - in-vitro and in-vivo studies

A study of the effects of three differentiating agents, butyric acid, retinoic acid and cytosine arabinoside on proliferation and differentiation of primary cultures, obtained from sixteen patients with myelo-proliferative disorder was conducted. The results showed that BA was an effective inhibitor of cell proliferation and inducer of cytodifferentiation. An acute non-lymphoblastic leukemia patient was treated with sodium butyrate. A temporary increase in differentiation-associated parameters were noted. However, the effects of SB were short-lived. The lack of clinical response led to the development of a BA prodrug pivaloyloxymethylbutyrate (AN-9). This prodrug was more potent in vitro than BA in the induction of cytodifferentiation and inhibition of cell proliferation.