Naringenin and Hesperidin as Promising Alternatives for Prevention and Co-Adjuvant Therapy for Breast Cancer

Abstract

Citrus (genus Citrus L.) fruits are essential sources of bioactive compounds with antioxidant properties, such as flavonoids. These polyphenolic compounds are divided into subclasses, in which flavanones are the most prominent. Among them, naringenin and hesperidin are emerging compounds with anticancer potential, especially for breast cancer (BC). Several mechanisms have been proposed, including the modulation of epigenetics, estrogen signaling, induction of cell death via regulation of apoptotic signaling pathways, and inhibition of tumor invasion and metastasis. However, this information is sparse in the literature and needs to be brought together to provide an overview of how naringenin and hesperidin can serve as therapeutic tools for drug development and as a successful co-adjuvant strategy against BC. This review detailed such mechanisms in this context and highlighted how naringenin and hesperidin could interfere in BC carcinogenesis and be helpful as potential alternative therapeutic sources for breast cancer treatment.

Keywords: anticancer activity; antioxidants; bioactive compounds; breast cancer; citrus fruits; flavanones; hesperidin; naringenin.

Figure 1

Naringenin and hesperidin derived from citrus fruits. Schematic representation of the sequential distribution of the major functional bioactive compounds (polyphenols, flavonoids, and flavanones) found in Citrus species and characterization of the molecular structure of the flavanone subclasses aglycone (naringenin) and glycoside (hesperidin).

Figure 2

Naringenin and hesperidin follow a common pathway through the phenylpropanoid pathway.

Figure 3

Schematic depiction of antitumor activity of naringenin and hesperidin.

Figure 4

Antimetastatic potential of naringenin and hesperidin. (1) The primary tumor is capable of metastasis under the influence of abnormal signaling pathways, such as increased expression of activator of transcription 3 (STAT3), transforming growth factor-β (TGF-β), pro-angiogenic factors, matrix metalloproteinases, and programmed death ligand 1 (PD-L1); (2) Administration of naringenin and hesperidin inhibited tumor cell migration by blocking these activated signals, which reverse the epithelial-mesenchymal transition (EMT) process and consequent loss of ability to disseminate.