Phytosterols activating nuclear receptors are involving in steroid hormone-dependent cancers: Myth or fact? - 04/12/23

Doi : 10.1016/j.biopha.2023.115783

Saad Bakrim ^a, Nasreddine El Omari ^b, Eman Jamil Khan ^c, Asaad Khalid ^d,^e,^⁎ , Ashraf N. Abdalla ^f, Jack Bee Chook ^g,^⁎ , Khang Wen Goh ^h , Long Chiau Ming ^g , Sara Aboulaghras ⁱ, Abdelhakim Bouyahya ^i,^⁎
^a Geo-Bio-Environment Engineering and Innovation Laboratory, Molecular Engineering, Biotechnology and Innovation Team, Polydisciplinary Faculty of Taroudant, Ibn Zohr University, Agadir 80000, Morocco
^b Laboratory of Histology, Embryology, and Cytogenetic, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat 10100, Morocco
^c Frontier Medical &amp, Dental College, Pakistan
^d Substance Abuse and Toxicology Research Center, Jazan University, P.O. Box: 114, Jazan 45142, Saudi Arabia
^e Medicinal and Aromatic Plants and Traditional Medicine Research Institute, National Center for Research, P. O. Box 2404, Khartoum, Sudan
^f Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia
^g School of Medical and Life Sciences, Sunway University, Sunway City, Malaysia
^h Faculty of Data Science and Information Technology, INTI International University, Nilai, Malaysia
ⁱ Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat 10106, Morocco

^⁎Corresponding author at: Substance Abuse and Toxicology Research Center, Jazan University, P.O. Box: 114, Jazan 45142, Saudi Arabia.Substance Abuse and Toxicology Research Center, Jazan UniversityP.O. Box: 114Jazan45142Saudi Arabia.^⁎⁎Corresponding authors.

Abstract

Nuclear receptors (NRs) represent intracellular proteins that function as a signaling network of transcriptional factors to control genes in response to a variety of environmental, dietary, and hormonal stimulations or serve as orphan receptors lacking a recognized ligand. They also play an essential role in normal development, metabolism, cell growth, cell division, physiology, reproduction, and homeostasis and function as biological markers for tumor subclassification and as targets for hormone therapy. NRs, including steroid hormone receptors (SHRs), have been studied as tools to examine the fundamentals of transcriptional regulation within the development of mammals and human physiology, in addition to their links to disturbances. In this regard, it is widely recognized that aberrant NR signaling is responsible for the pathological growth of hormone-dependent tumors in response to SHRs dysregulation and consequently represents a potential therapeutic candidate in a range of diseases, as in the case of prostate cancer and breast cancer. On the other hand, phytosterols are a group of plant-derived compounds that act directly as ligands for NRs and have proven their efficacy in the management of diabetes, heart diseases, and cancers. However, these plants are not suggested in cases of hormone-dependent cancer since a certain group of plants contains molecules with a chemical structure similar to that of estrogens, which are known as phytoestrogens or estrogen-like compounds, such as lignans, coumestans, and isoflavones. Therefore, it remains an open and controversial debate regarding whether consuming a phytosterol-rich diet and adopting a vegetarian lifestyle like the Mediterranean diet may increase the risk of developing steroid hormone-dependent cancers by constitutively activating SHRs and thereby leading to tumor transformation. Overall, the purpose of this review is to better understand the relevant mechanistic pathways and explore epidemiological investigations in order to establish that phytosterols may contribute to the activation of NRs as cancer drivers in hormone-dependent cancers.

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Keywords : Nuclear receptors, Phytosterols, Hormone-dependent cancers, Vegetarian diets, Steroid hormone receptors, Prostate cancer, Breast cancer