β-Ionone Induces Cell Cycle Arrest and Apoptosis in Human Prostate Tumor Cells

3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase is the rate-limiting activity in the mevalonate pathway that provides essential intermediates for posttranslational modification of growth-associated proteins. Assorted dietary isoprenoids found in plant foods suppress HMG CoA reductase and have cancer chemopreventive activity. -Ionone, a cyclic sesquiterpene and an end-ring analog of -carotene, induced concentration-dependent inhibition of the proliferation of human DU145 (IC50 = 210mol/L) and LNCaP (IC50 = 130mol/L) prostate carcinoma cells and PC-3 prostate adenocarcinoma cells (IC50 = 130mol/L). Concomitantly, -ionone-induced apoptosis and cell cycle arrest at the G1 phase in DU145 and PC-3 cells were shown by fluorescence microscopy, flow cytometry, and TUNEL reaction, and downregulation of cyclin-dependent kinase 4 (Cdk4) and cyclin D1 proteins. Growth suppression was accompanied by -ionone-induced downregulation of reductase protein. A blend of -ionone (150mol/L) and trans, trans-farnesol (25mol/L), an acyclic sesquiterpene that putatively initiates the degradation of reductase, suppressed the net growth of DU145 cells by 73%, an impact exceeding the sum of those of -ionone (36%) and farnesol (22%), suggesting a synergistic effect. -ionone, individually or in combination with other HMG CoA reductase suppressors, may have potential in prostate cancer chemoprevention and/or therapy.