Lea Michael A, Shareef Asif, Sura Monali, desBordes Charles
Department of Biochemistry and Molecular Biology, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.
Cancer Chemother Pharmacol. 2004 Jul;54(1):57-63. doi: 10.1007/s00280-004-0782-5. Epub 2004 Mar 19.
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.
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.
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.
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.
进行了一项构效关系研究，以确定苯基链烷酸的侧链长度和苯基链烯酸的不饱和度对组蛋白乙酰化诱导及癌细胞增殖抑制的影响。
使用DS19小鼠红白血病细胞、PC-3人前列腺癌细胞和Caco-2人结肠癌细胞进行细胞增殖研究。比较了4-苯基丁酸及结构相关分子对组蛋白脱乙酰酶的作用和组蛋白乙酰化的诱导情况。
随着碳链长度在4至10个碳之间增加，观察到苯基链烷酸对细胞增殖的抑制作用增强，同时处于S期的细胞减少，凋亡细胞增加。在侧链中引入双键与生长抑制增强相关。相比之下，4-苯基丁酸比所检测的其他苯基链烷酸是更有效的组蛋白脱乙酰酶抑制剂和组蛋白乙酰化诱导剂。
与4-苯基丁酸的作用相比，对于长链苯基链烷酸和苯基链烯酸的生长抑制，除抑制组蛋白脱乙酰酶以外的作用似乎更为重要。
