d-Limonene: a bioactive food component from citrus and evidence for a potential role in breast cancer prevention and treatment

Abstract

Although limited, observations from cell culture, animal, and epidemiological studies support the presence of anti-cancer properties in citrus peel and the primary bioactive food constituent, d-limonene. Early evidence from animal models suggests that when ingested, d-limonene exhibits a wide spectrum of biologic activity including chemotherapeutic and chemopreventive effects. In some of these early models, an analog of d-limonene, perillyl alcohol, demonstrated a more potent effect than d-limonene itself. Yet, when perillyl alcohol advanced to clinical trials, several trials were ended early due to doselimiting toxicities. Alternatively, oral d-limonene administration in humans is well tolerated even at high doses supporting its investigation as a potential bioactive for cancer prevention. Though the exact mechanisms of action of d-limonene are unclear, immune modulation and antiproliferative effects are commonly reported. Here, we review the pre-clinical evidence for d-limonene's anticancer mechanisms, bioavailability, and safety, as well as the evidence for anti-cancer effects in humans, focusing on studies relevant to its use in the prevention and treatment of breast cancer.

Variation Patterns of the Volatile Compounds in Flowers of Chinese Native Citrus Species and Their Taxonomic Implications

“…Similar results were observed in Changshanhuyou. In this study, a very close variation pattern of flower volatiles was found in Ningmeng 4 and its proposed parents, which further confirmed the hypothesis that rough lemon is a cross between citron and mandarin (Miller et al 2011;Rossi et al 2013).…”

“…Citrus fruits are popular food items because of their beautiful colors, pleasant flavors, and rich nutritional components (Tripoli et al 2007). Citrus fruits can be consumed fresh or be processed into desserts, juices and jams and are good resources of vitamin C, folic acid, flavonoids, dietary fiber and many other health-promoting substances (Miller et al 2011). In the food industry, citrus processing produces an enormous amount of byproducts, such as pomace, which represents 50% of the raw fruits and is a good source of volatile compounds (Anwar et al 2008;Omori et al 2011).…”

Free and Bound Volatile Compounds in Juice and Peel of Eureka Lemon

“…The luxuriant aroma compounds of lemon are applied in many fields. d-Limonene plays a potential role in preventing breast cancer (Miller et al, 2011), and the antioxidant activity of lemon essential oils has been confirmed (Di et al, 2010). Lemon products are also important for food industry and health care (González-Molina et al, 2010).…”

New Targets for the Identification of an Anti-Inflammatory Anti-Senescence Activity

“…In confirmation to our in vitro results, the capacity of geraniol (AISA 5202-G) to inhibit the adhesion of leukocytes following TNF- stimulation had already been established. As for d-Limonene, in consideration of the efficacy of its metabolite, perillyl alcohol (POH), already tested in clinical trials in patients with refractory solid malignancies (Miller et al, 2011), it seems plausible that it plays the role of a precursor. In conclusion, the complex sequence of events of the inflammatory response including endothelial adhesion molecule expression for the vascular recruitment of leukocytes to the site of injury, concomitant with actin polymerization challenges the signaling pathway of the rho GTPase family (Xu et al, 2009;Burridge & Wennerberg, 2004;Millan & Ridley, 2005;Dillon & Goda, 2005).…”