4.7 Review

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

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Article Biochemistry & Molecular Biology

Two Argan Oil Phytosterols, Schottenol and Spinasterol, Attenuate Oxidative Stress and Restore LPS-Dysregulated Peroxisomal Functions in Acox1-/- and Wild-Type BV-2 Microglial Cells

Soukaina Essadek et al.

Summary: Studies have shown that two major phytosterols, Schottenol and Spinasterol, found in argan oil can attenuate oxidative stress, inflammation, and peroxisome dysfunction in mouse brains. In an experiment using LPS-activated microglial cells, these phytosterols decreased ROS production and NO release, and inhibited the expression of inflammatory genes and proteins. Additionally, they enhanced antioxidant activity and protected peroxisomal functions in microglial cells.

ANTIOXIDANTS (2023)

Review Biochemistry & Molecular Biology

New insights into the suppression of inflammation and lipid accumulation by JAZF1

Wujun Chen et al.

Summary: Atherosclerosis is a major global health issue, and the identification of new therapeutic targets and agents is crucial. The gene JAZF1 has been found to play a role in suppressing inflammation and reducing lipid accumulation in adipose tissue. It acts by inhibiting NF-kB pathway activation and immune cell infiltration, and regulating genes involved in cytokine and lipid metabolism.

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Nuclear Receptor Imaging In Vivo-Clinical and Research Advances

Ephraim E. Parent et al.

Summary: Nuclear receptors are transcription factors involved in physiology and diseases. Noninvasive imaging of nuclear receptors using radiolabeled ligands and PET can be used clinically to identify metastatic sites for drug therapy and for research on drug development and receptor function. This mini-review focuses on PET imaging of estrogen, progesterone, and androgen receptors in breast and prostate cancer.

JOURNAL OF THE ENDOCRINE SOCIETY (2023)

Review Chemistry, Medicinal

The critical role of the phytosterols in modulating tumor microenvironment via multiple signaling: A comprehensive molecular approach

Ashraf Ullah Khan et al.

Summary: Cancer is a major global health issue, with increasing cases each year. The development of cancer is influenced by various factors such as radiation, lifestyle, smoking, environment, and genetics. The cell cycle, regulated by molecular signaling proteins, is disrupted when these proteins are altered, affecting cellular growth and proliferation. Natural products, including phytosterols, have shown promising anti-cancer activities by modulating molecular signaling pathways involved in the tumor microenvironment. Further research is required to establish the clinical efficacy and safety of phytosterols.

PHYTOTHERAPY RESEARCH (2023)

Article Nutrition & Dietetics

Dietary phytoestrogens and total and cause-specific mortality: results from 2 prospective cohort studies

Zhangling Chen et al.

Summary: This study examines the associations between intake of isoflavones, lignans, and coumarins and total and cause-specific mortality in US males and females. Results showed that higher intake of total phytoestrogens was associated with lower risk of total cardiovascular disease (CVD) and non-CVD/noncancer mortality. Individual phytoestrogens were also significantly associated with lower risk of CVD mortality and other types of mortality.

AMERICAN JOURNAL OF CLINICAL NUTRITION (2023)

Article Chemistry, Medicinal

Understanding the Phytoestrogen Genistein Actions on Breast Cancer: Insights on Estrogen Receptor Equivalence, Pleiotropic Essence and Emerging Paradigms in Bioavailability Modulation

Parth Malik et al.

Summary: Genistein, a major phenolic ingredient of soy and soy products, is a recognized phytoestrogen with interaction ability with estrogen receptors (ERs). Its metabolic conversion from genistin to genistein by gut microbes and intestinal enzymes enhances its absorption. It interferes in breast cancer development via multiple actions on cell proliferation, survival, angiogenesis, and apoptosis. However, its efficacy in clinical trials and its equivalence to 17-beta-estradiol (E2) have been questioned. Factors such as intake mode, ER expression pattern, the ratio of ERa and ER beta, patient age, and menopausal status affect its breast cancer activities.

CURRENT TOPICS IN MEDICINAL CHEMISTRY (2023)

Article Food Science & Technology

LXRs/ABCA1 activation contribute to the anti-inflammatory role of phytosterols on LPS-induced acute lung injury

Daxue He et al.

Summary: The study found that phytosterols can partially alleviate pulmonary inflammation in LPS-induced acute lung injury (ALI) by activating the LXRs/ABCA1 pathway.

JOURNAL OF FUNCTIONAL FOODS (2022)

Review Oncology

Nuclear Receptor Coregulators in Hormone-Dependent Cancers

Hedieh Jafari et al.

Summary: Alterations in coregulators of nuclear receptor signaling are closely linked to hormone-dependent cancers, understanding how these factors modulate receptor activity can lead to better diagnostic and therapeutic approaches.

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Arisaema heterophyllum Blume Monomer Stigmasterol Targets PPAR gamma and Inhibits the Viability and Tumorigenicity of Lung Adenocarcinoma Cells NCI-H1975

Na Song et al.

Summary: This study elucidates the regulatory effect and molecular mechanism of the monomer stigmasterol from Arisaema heterophyllum Blume on lung adenocarcinoma cells. The results reveal that stigmasterol inhibits cell viability, promotes lipid deposition, and influences cell proliferation and tumorigenesis by modulating the expression of cyclins and PPAR gamma signaling pathway proteins. Tumor formation experiments confirm that stigmasterol significantly reduces tumor size and weight. Therefore, stigmasterol may have potential as a therapeutic agent for lung adenocarcinoma.

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Article Chemistry, Medicinal

4-Hydroxybenzoic Acid and β-Sitosterol from Cucurbita ficifolia Act as Insulin Secretagogues, Peroxisome Proliferator-Activated Receptor-Gamma Agonists, and Liver Glycogen Storage Promoters: In Vivo, In Vitro, and In Silico Studies

Wendoline Rosiles-Alanis et al.

Summary: Insulin secretion and GLUT4 expression are critical in glucose regulation. Cucurbita ficifolia fruit, used in traditional medicine for diabetes control, contains compounds that have multiple antidiabetic effects. This study isolated and identified beta-sitosterol and 4-hydroxybenzoic acid as potential compounds with antidiabetic properties.

JOURNAL OF MEDICINAL FOOD (2022)

Article Endocrinology & Metabolism

Importins involved in the nuclear transportation of steroid hormone receptors: In silico and in vitro data

Konstantina Kalyvianaki et al.

Summary: The nuclear receptor superfamily (NRS) is a family of 48 receptors that receive signals from lipophilic substances, with subfamily 3 including steroid hormone receptors. The structure of nuclear receptors usually consists of activating domains, DNA-binding domains, ligand-binding domains, and hinge regions. The hinge region, which contains a nuclear localization signal (NLS), is responsible for nuclear transport. Importins 4, 5, and 7 have been identified as alternative transporters for steroid hormone receptors.

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Review Pharmacology & Pharmacy

Liver X receptor: a potential target in the treatment of atherosclerosis

Shreya R. Savla et al.

Summary: LXRs are important regulators of atherosclerosis and understanding their role is important for developing potential therapeutics. This review discusses the role of LXRs in atherosclerotic development, LXR agonists, and future research directions. It highlights the need for further research on specific agonist-targeted LXR isoforms and cell type-specific knockout models.

EXPERT OPINION ON THERAPEUTIC TARGETS (2022)

Editorial Material Biochemical Research Methods

Nuclear receptors: from molecular mechanisms to therapeutics

Daniel E. Frigo et al.

Summary: Nuclear receptors are ligand-activated transcription factors that regulate key functions in reproduction, development, and physiology. Dysregulation of these receptors is often linked to diseases. Most nuclear receptors can be selectively activated or inactivated by small molecules, making them prominent therapeutic targets.

EXPLORING NUCLEAR RECEPTORS (2021)

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Phytosterols: Potential Metabolic Modulators in Neurodegenerative Diseases

Niti Sharma et al.

Summary: Phytosterols, a class of natural products, are crucial components in diet and have various applications in foods, cosmetics, and herbal medicines. Stigmasterol and beta-sitosterol are common types of phytosterols with significant activities related to neurodegenerative diseases. This mini-review provides an overview of research on selected phytosterols associated with neurodegenerative diseases, covering major phytosterols and their biological activities.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Bile acids and their receptors in metabolic disorders

Stefano Fiorucci et al.

Summary: Bile acids play a crucial role in regulating metabolic processes by integrating their signaling with other receptors in a time-ordered manner synchronized by circadian rhythm. The last decade has seen challenges in developing systemic FXR agonists, with the emergence of intestinal-restricted and dual FXR/GPBAR1 agonists as potential alternatives.

PROGRESS IN LIPID RESEARCH (2021)

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Current and emerging estrogen receptor-targeted therapies for the treatment of breast cancer

Corinne N. Haines et al.

Summary: Nearly 80% of breast cancers are ER+ and depend on estrogen signaling for growth, making endocrine therapies essential. Resistance to current therapies is a major challenge, highlighting the need for new strategies to target ER+ disease effectively.

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Influence of Diet and Nutrition on Prostate Cancer

Makoto Matsushita et al.

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Stigmasterol stimulates transintestinal cholesterol excretion independent of liver X receptor activation in the small intestine

Hannah C. Lifsey et al.

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Tetsuji Moriyama et al.

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Plants are Capable of Synthesizing Animal Steroid Hormones

Danuse Tarkowska

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Nuclear receptors in cancer - uncovering new and evolving roles through genomic analysis

Vineet K. Dhiman et al.

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C24-hydroxylated stigmastane derivatives as Liver X Receptor agonists

Francisco Fermin Castro Navas et al.

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Recent Advances in the Medicinal Chemistry of Liver X Receptors

Bahaa El-Dien M. El-Gendy et al.

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Side-Chain Modified Ergosterol and Stigmasterol Derivatives as Liver X Receptor Agonists

Maura Marinozzi et al.

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Effects of ginseng on two main sex steroid hormone receptors: estrogen and androgen receptors

Joonwoo Park et al.

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Enas Mahmoud Moustafa et al.

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Naiyer Shahzad et al.

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Integrative Clinical Genomics of Advanced Prostate Cancer

Dan Robinson et al.

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Target selection for FDA-approved medicines

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Phytosterol oxidation products in enriched foods: Occurrence, exposure, and biological effects

Birgit Scholz et al.

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Microtubule-targeting agents are clinically successful due to both mitotic and interphase impairment of microtubule function

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24(S)-Saringosterol from Edible Marine Seaweed Sargassum fusiforme Is a Novel Selective LXRβ Agonist

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Negative Regulation of Estrogen Signaling by ERβ and RIP140 in Ovarian Cancer Cells

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Piperine, a Component of Black Pepper, Inhibits Adipogenesis by Antagonizing PPARγ Activity in 3T3-L1 Cells

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Phytosterols as anticancer compounds

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Importin 13 regulates nuclear import of the glucocorticoid receptor in airway epithelial cells

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Phytoestrogens and breast cancer - promoters or protectors?

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Susan E. McCann et al.

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Effect of dietary intake of phytoestrogens on estrogen receptor status in premenopausal women with breast cancer

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Estrogen bioactivity in fo-ti and other herbs used for their estrogen-like effects as determined by a recombinant cell bioassay

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Soy, isoflavones, and breast cancer risk in Japan

S Yamamoto et al.

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M Hussain et al.

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H Adlercreutz

LANCET ONCOLOGY (2002)

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PJD Bouic

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