Recent Progress in Discovering the Role of Carotenoids and Their Metabolites in Prostatic Physiology and Pathology with a Focus on Prostate Cancer-A Review-Part I: Molecular Mechanisms of Carotenoid Action

Abstract

Among the vast variety of plant-derived phytochemicals, the group of carotenoids has continuously been investigated in order to optimize their potential application in the area of dietary intervention and medicine. One organ which has been especially targeted in many of these studies and clinical trials is the human prostate. Without doubt, carotenoids (and their endogenous derivatives-retinoids and other apo-carotenoids) are involved in intra- and intercellular signaling, cell growth and differentiation of prostate tissue. Due to the accumulation of new data on the role of different carotenoids such as lycopene (LC) and β-carotene (BC) in prostatic physiology and pathology, the present review aims to cover the past ten years of research in this area. Data from experimental studies are presented in the first part of the review, while epidemiological studies are disclosed and discussed in the second part. The objective of this compilation is to emphasize the present state of knowledge regarding the most potent molecular targets of carotenoids and their main metabolites, as well as to propose promising carotenoid agents for the prevention and treatment of prostatic diseases.

Keywords: carotenoids; metabolism; nuclear receptors; prostate cancer; retinoids; transcription factors; xanthophylls.

Figure 1

Main metabolic pathway of carotenoids. (A) The structure of carotenoids. (B) The process of absorption and metabolism of carotenoids. (C) The main intracellular targets of carotenoids.

Figure 2

The molecular pathways of carotenoid action in PC (discussed in Section 5), which have been the subject of research in the last decade. They involve the growth factor receptors (i.e., epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor (IGFR)), ABC transporters, molecules of intracellular adhesion (i.e., ICAM-1). Moreover, a variety of proteins, which control the cell cycle and process of apoptosis, change their level under the influence of carotenoids. Significant changes were discovered, as well in the components of extracellular matrix (i.e., matrix metalloproteases (MMPs) and kallikreins (KLKs)). More detailed information of given carotenoids on the particular factors from this figure is shown in Table 4 (the factors marked with red color are not directly reviewed in our work; however they are necessary to understand their relation to well-established functions, e.g., mTOR).