Abstract
Hydroquinone, an activator of caspase-9 activity via reactive oxygen species, and farnesol, a post-translational down-regulator of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity suppress the growth of murine B16 melanoma cells. Our previous studies have shown that famesyl-O-acetylhydroquinone has a markedly greater growth-suppressive activity than that predicted by the responses to the parent compounds. Perillyl alcohol, a modulator of small G-protein activity, and bipheryl compounds, activators of Fas-mediated death pathways, suppress B16 growth. A similar synergistic increase in the potency of each compound when ether-linked to acetylhydroquinone is reported. Perillyl-O-acelylhydroquinone, biphenylethyl-O-acetylhydroquinone and biphenylpropyl-O-acetylhydroquinone had dose-dependent impacts on the proliferation of B16 cells with 50% inhibitory concentration (IC50) values of 8.0, 4.2 and 1.4 mu mol/L, respectively. The growth-suppression effected by bipherylpropyl-O-acetylhydroquinone was accompanied by a dose-dependent arrest at the G1/S interface of the cell cycle, an impact greater than that previously reported for famesyl-O-acetylhydroquinone (IC50=2.5 mu mol/L). These new hydroquinone derivatives may have potential in cancer chentoprevention and/or therapy.