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

Abstract

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. β-Ionone, a cyclic sesquiterpene and an end-ring analog of β-carotene, induced concentration-dependent inhibition of the proliferation of human DU145 (IC₅₀ = 210 μmol/L) and LNCaP (IC₅₀ = 130 μmol/L) prostate carcinoma cells and PC-3 prostate adenocarcinoma cells (IC₅₀ = 130 μmol/L). Concomitantly, β-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 β-ionone-induced downregulation of reductase protein. A blend of β-ionone (150 μmol/L) and trans, trans-farnesol (25 μmol/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 β-ionone (36%) and farnesol (22%), suggesting a synergistic effect. β-ionone, individually or in combination with other HMG CoA reductase suppressors, may have potential in prostate cancer chemoprevention and/or therapy.

ACKNOWLEDGEMENT

This research was supported by Texas Department of Agriculture, Texas Woman's University Research Enhancement Program, Summer Stipend Program, Faculty Development Fund and Human Nutrition Research Fund. We thank Dr. DiAnna Hynds of the Department of Biology, Texas Woman's University for her technical assistance in fluorescence microscopy.

Sheila Jones is now with the Department of Kinesiology and Nutrition, Abilene Christian University, Abilene, TX, USA. Nicolle V. Fernandes is now with the Department of Family and Consumer Sciences, Ball State University, Muncie, IN, USA. Rajasekhar Katuru is now with the Baton Rouge General Medical Center, Baton Rouge, LA, USA.