4-Fluoro-N-butylphenylacetamide (H6) inhibits cell growth via cell-cycle arrest and apoptosis in human cervical cancer cells

Phenylacetate induced tumor cytostasis and differentiation. The chemotherapeutic function of the compound in lung cancer has been previously reported, however, whether or not phenylacetate performs other activities is not known. In this study, the potential usage of synthetic phenylacetate derivatives, 4-fluoro-N-butylphenylacetamides (H6) was investigated in human cervical cancer cells. H6 displayed anti-proliferative and apoptosis effects, with an IC50 of 1.0-1.5 mM and an ID50 of about 3 days. Moreover, it significantly induced apoptosis as evidenced by morphological changes, DAPI and TUNEL staining and DNA fragmentation. H6 increased the expression of Bax protein, whereas it decreased the expression of Bcl-2 protein. H6 also induced accumulation of cytosolic cytochrome c and activation of caspase cascade (caspase-9 and -3), and then DNA fragmentation and apoptosis occurred. The underlying anti-proliferative mechanism for H6 is likely due to the down-regulation of G2/M-phase association cdks and cyclins and up-regulation of p53 to mediate G2/M-phase arrest. Furthermore, the decrease of Bcl-2 and activation of Bax, caspase-9/caspase-3 may be the effectors of H6-induced apoptosis.