Human breast tissue disposition and bioactivity of limonene in women with early-stage breast cancer

Jessica A. Miller, Julie E. Lang, Michele Ley, Raymond B Nagle, Chiu-Hsieh Hsu, Patricia A. Thompson, Catherine Cordova, Amy L Waer, Hsiao-Hui Chow

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Limonene is a bioactive food component found in citrus peel oil that has shown chemopreventive and chemotherapeutic activities in preclinical studies. We conducted an open-label pilot clinical study to determine the human breast tissue disposition of limonene and its associated bioactivity. We recruited 43 women with newly diagnosed operable breast cancer electing to undergo surgical excision to take 2 grams of limonene daily for two to six weeks before surgery. Blood and breast tissue were collected to determine drug/metabolite concentrations and limonene-induced changes in systemic and tissue biomarkers of breast cancer risk or carcinogenesis. Limonene was found to preferentially concentrate in the breast tissue, reaching high tissue concentration (mean = 41.3 μg/g tissue), whereas the major active circulating metabolite, perillic acid, did not concentrate in the breast tissue. Limonene intervention resulted in a 22% reduction in cyclin D1 expression (P = 0.002) in tumor tissue but minimal changes in tissue Ki67 and cleaved caspase-3 expression. No significant changes in serum leptin, adiponectin, TGF-β1, insulin-like growth factor binding protein-3 (IGFBP-3), and interleukin-6 (IL-6) levels were observed following limonene intervention. There was a small but statistically significant postintervention increase in insulin-like growth factor I (IGF-I) levels. We conclude that limonene distributed extensively to human breast tissue and reduced breast tumor cyclin D1 expression that may lead to cell-cycle arrest and reduced cell proliferation. Furthermore, placebo-controlled clinical trials and translational research are warranted to establish limonene's role for breast cancer prevention or treatment.

Original languageEnglish (US)
Pages (from-to)577-584
Number of pages8
JournalCancer Prevention Research
Volume6
Issue number6
DOIs
StatePublished - Jun 2013

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Breast
Breast Neoplasms
Cyclin D1
limonene
Insulin-Like Growth Factor Binding Protein 3
Translational Medical Research
Citrus
Adiponectin
Controlled Clinical Trials
Leptin
Cell Cycle Checkpoints
Insulin-Like Growth Factor I
Caspase 3
Interleukin-6
Oils
Carcinogenesis
Biomarkers
Placebos
Cell Proliferation
Food

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Human breast tissue disposition and bioactivity of limonene in women with early-stage breast cancer. / Miller, Jessica A.; Lang, Julie E.; Ley, Michele; Nagle, Raymond B; Hsu, Chiu-Hsieh; Thompson, Patricia A.; Cordova, Catherine; Waer, Amy L; Chow, Hsiao-Hui.

In: Cancer Prevention Research, Vol. 6, No. 6, 06.2013, p. 577-584.

Research output: Contribution to journalArticle

Miller, Jessica A. ; Lang, Julie E. ; Ley, Michele ; Nagle, Raymond B ; Hsu, Chiu-Hsieh ; Thompson, Patricia A. ; Cordova, Catherine ; Waer, Amy L ; Chow, Hsiao-Hui. / Human breast tissue disposition and bioactivity of limonene in women with early-stage breast cancer. In: Cancer Prevention Research. 2013 ; Vol. 6, No. 6. pp. 577-584.
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