β-ionone induces cell cycle arrest and apoptosis in human prostate tumor cells

Sheila Jones, Nicolle V. Fernandes, Hoda Yeganehjoo, Rajasekhar Katuru, Haibin Qu, Zhiling Yu, Huanbiao Mo

Research output: Contribution to journalArticle

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)600-610
Number of pages11
JournalNutrition and Cancer
Volume65
Issue number4
DOIs
Publication statusPublished - May 1 2013

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ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Oncology
  • Nutrition and Dietetics
  • Cancer Research

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