Plasma Metabolomic Profiles of Breast Cancer Patients after Short-term Limonene Intervention

Abstract

Limonene is a lipophilic monoterpene found in high levels in citrus peel. Limonene demonstrates anti-cancer properties in preclinical models with effects on multiple cellular targets at varying potency. While of interest as a cancer chemopreventive, the biological activity of limonene in humans is poorly understood. We conducted metabolite profiling in 39 paired (pre/post-intervention) 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 ultra-performance liquid chromatography (UPLC) coupled to a linear trap quadrupole (LTQ) system and gas chromatography mass spectrometry (GC-MS). 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 (HMDB) 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’s<0.01), and significant increases in bile acids (P’s≤0.05) and multiple collagen breakdown products (P’s<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’s≤0.05). Here, oral administration of limonene resulted in significant changes in several metabolic pathways. Further, 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.

Metabolomic profiling of amines in sepsis predicts changes in NOS canonical pathways

“…Proteins were removed from plasma samples by precipitation with isopropanol (0.1% formic acid). Amines were measured using a HSS T3 UHPLC column system (Waters, Milford, MA, USA) connected to a Xevo TQ-S tandem quadrupole mass spectrometer (Waters, Wilmslow, UK) [ 23 , 24 ]. Isotopically labelled standards (10μg/ml) and calibration curves (Sigma; 1–400μM) were used for quantification.…”

Dendrobium officinale Kimura et Migo: A Review on Its Ethnopharmacology, Phytochemistry, Pharmacology, and Industrialization

“…The content of limonene (123) in the stem is 9.15% for the second; limonene is most abundant in the leaves, accounting for 38% [44]. Limonene contains anticancer properties with effects on multiple cellular targets in preclinical models [45]. Dendrobium officinale containing a high content of (E)-2-hexenal (106) shows bactericidal activity against Pseudococcus viburni , Pseudococcus affinis , Bemisia sp., and Frankliniella occidentalis [46].…”

Novel personalized pathway-based metabolomics models reveal key metabolic pathways for breast cancer diagnosis

“…This could be due to various reasons, such as the heterogeneity of the populations and small study sizes, variability of the experimental protocols, and technical noise in the metabolomics data. In fact, we compared the multiple studies that had attempted to identify metabolites in blood as biomarkers for breast cancer previously [ 34 , 46 – 48 ] and found little overlap or even controversies among them (Additional file 2 : Figure S5) [ 13 , 34 , 35 , 47 – 52 ]. On the contrary, many metabolites in the featured pathways that we have found with our method coincide with previous reports, such as increases in alanine, pyruvate, and lactate as well as decreases in choline in cancer samples.…”