Plasma metabolomic profiles of breast cancer patients after short-term limonene intervention

Jessica A. Miller, Kirk Pappan, Patricia A. Thompson, Elizabeth J. Want, Alexandros P. Siskos, Hector C. Keun, Jacob Wulff, Chengcheng Hu, Julie E. Lang, Hsiao-Hui Chow

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Limonene is a lipophilic monoterpene found in high levels in citrus peel. Limonene demonstrates anticancer properties in preclinical models with effects on multiple cellular targets at varying potency. While of interest as a cancer chemopreventive, the biologic activity of limonene in humans is poorly understood. We conducted metabolite profiling in 39 paired (pre/postintervention) plasma samples from early-stage breast cancer patients receiving limonene treatment (2 g QD) before surgical resection of their tumor. Metabolite profiling was conducted using ultraperformance liquid chromatography coupled to a linear trap quadrupole system and gas chromatography-mass spectrometry. Metabolites were identified by comparison of ion features in samples to a standard reference library. Pathway-based interpretation was conducted using the human metabolome database and the MetaCyc database. Of the 397 named metabolites identified, 72 changed significantly with limonene intervention. Class-based changes included significant decreases in adrenal steroids (P < 0.01), and significant increases in bile acids (P ≤ 0.05) and multiple collagen breakdown products (P < 0.001). The pattern of changes also suggested alterations in glucose metabolism. There were 47 metabolites whose change with intervention was significantly correlated to a decrease in cyclin D1, a cell-cycle regulatory protein, in patient tumor tissues (P ≤ 0.05). Here, oral administration of limonene resulted in significant changes in several metabolic pathways. Furthermore, pathway-based changes were related to the change in tissue level cyclin D1 expression. Future controlled clinical trials with limonene are necessary to determine the potential role and mechanisms of limonene in the breast cancer prevention setting.

Original languageEnglish (US)
Pages (from-to)86-93
Number of pages8
JournalCancer Prevention Research
Volume8
Issue number1
DOIs
StatePublished - Jan 1 2015

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Metabolomics
Breast Neoplasms
Cyclin D1
Databases
Neoplasms
Cell Cycle Proteins
Monoterpenes
Metabolome
limonene
Citrus
Controlled Clinical Trials
Metabolic Networks and Pathways
Bile Acids and Salts
Liquid Chromatography
Gas Chromatography-Mass Spectrometry
Libraries
Oral Administration
Collagen
Steroids
Ions

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Plasma metabolomic profiles of breast cancer patients after short-term limonene intervention. / Miller, Jessica A.; Pappan, Kirk; Thompson, Patricia A.; Want, Elizabeth J.; Siskos, Alexandros P.; Keun, Hector C.; Wulff, Jacob; Hu, Chengcheng; Lang, Julie E.; Chow, Hsiao-Hui.

In: Cancer Prevention Research, Vol. 8, No. 1, 01.01.2015, p. 86-93.

Research output: Contribution to journalArticle

Miller, JA, Pappan, K, Thompson, PA, Want, EJ, Siskos, AP, Keun, HC, Wulff, J, Hu, C, Lang, JE & Chow, H-H 2015, 'Plasma metabolomic profiles of breast cancer patients after short-term limonene intervention', Cancer Prevention Research, vol. 8, no. 1, pp. 86-93. https://doi.org/10.1158/1940-6207.CAPR-14-0100
Miller, Jessica A. ; Pappan, Kirk ; Thompson, Patricia A. ; Want, Elizabeth J. ; Siskos, Alexandros P. ; Keun, Hector C. ; Wulff, Jacob ; Hu, Chengcheng ; Lang, Julie E. ; Chow, Hsiao-Hui. / Plasma metabolomic profiles of breast cancer patients after short-term limonene intervention. In: Cancer Prevention Research. 2015 ; Vol. 8, No. 1. pp. 86-93.
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