Induction of histone acetylation and inhibition of growth by phenyl alkanoic acids and structurally related molecules.
OBJECTIVE
A structure-activity study was undertaken to determine the influence of side chain length of phenyl alkanoic acids and the degree of unsaturation of phenyl alkenoic acids on the induction of histone acetylation and inhibition of cancer cell proliferation.


METHODS
Studies on cell proliferation were performed with DS19 mouse erythroleukemic cells, PC-3 human prostate cancer cells and Caco-2 human colon cancer cells. Actions on histone deacetylase and the induction of histone acetylation were compared for 4-phenylbutyrate and structurally related molecules.


RESULTS
Increasing inhibition of cell proliferation by phenyl alkanoic acids together with a decrease in cells in S phase and an increase in apoptotic cells was observed with increased chain length between four and ten carbons. Introduction of double bonds into the side chain was associated with increased growth inhibition. In contrast, 4-phenylbutyrate was a more potent inhibitor of histone deacetylase and inducer of histone acetylation than the other phenyl alkanoic acids examined.


CONCLUSIONS
In comparison with the action of 4-phenylbutyrate, actions other than inhibition of histone deacetylase appear to be more important for growth inhibition by longer chain phenyl alkanoic and phenyl alkenoic acids.
Lea
Michael A
MA
Department of Biochemistry and Molecular Biology, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA. lea@umdnj.edu
Shareef
Asif
A
Sura
Monali
M
desBordes
Charles
C
D000107:Acetylation; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D003110:Colonic Neoplasms / Q000473:pathology*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D008297:Male; D051379:Mice; D010654:Phenylbutyrates / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D013329:Structure-Activity Relationship
D006657:Histones; D010654:Phenylbutyrates; C075773:4-phenylbutyric acid