Abstract
A high proportion (∼40%) of breast cancers are hormone-dependent and it is the female hormone estradiol (E2) that is believed to play a key role in the initiation, promotion and progression of this disease. In the fight against this disease, compounds which are potent inhibitors of the cytochrome P-450 enzyme aromatase (AR) (which catalyses the conversion of the C19 androgens to the C18 estrogens) have been the major target. However, the administration of AR inhibitors alone does not prevent the localised biosynthesis of estrone (E1) (and therefore the subsequent synthesis of E2) within breast tumour cells via alternative non-AR routes. This has therefore been the major impetus for the development of steroid sulfatase (E1STS) inhibitors. The E1STS enzyme regulates the formation of E1 from estrone sulfate (E1S), a steroid conjugate present in high concentrations in tissue and blood in women with breast cancer. The STS enzyme has also been shown to catalyse the formation of dehydroepiandrosterone (DHEA) from DHEA-sulfate (DHEAS). This is important since DHEA can be converted to 5-androstene-3β,17β-diol, which has been shown to possess weak estrogenic properties, however, due to the high concentration of this steroid, it is able to stimulate the growth of breast cancer cells in vitro and in vivo. Considerable progress has been made in recent years in the development of a number of potent E1STS inhibitors, as such both steroidal and non-steroidal compounds have been considered and a number of highly potent inhibitors have been produced and evaluated against what is now considered a crucial enzyme in the fight against hormone-dependent breast cancer. The review therefore summarises the work that has been undertaken todate.
Anti-Cancer Agents in Medicinal Chemistry
Title: Estrone Sulfatase and Its Inhibitors
Volume: 9 Issue: 6
Author(s): Kwabina Aidoo-Gyamfi, Tim Cartledge, Kruti Shah and Sabbir Ahmed
Affiliation:
Abstract: A high proportion (∼40%) of breast cancers are hormone-dependent and it is the female hormone estradiol (E2) that is believed to play a key role in the initiation, promotion and progression of this disease. In the fight against this disease, compounds which are potent inhibitors of the cytochrome P-450 enzyme aromatase (AR) (which catalyses the conversion of the C19 androgens to the C18 estrogens) have been the major target. However, the administration of AR inhibitors alone does not prevent the localised biosynthesis of estrone (E1) (and therefore the subsequent synthesis of E2) within breast tumour cells via alternative non-AR routes. This has therefore been the major impetus for the development of steroid sulfatase (E1STS) inhibitors. The E1STS enzyme regulates the formation of E1 from estrone sulfate (E1S), a steroid conjugate present in high concentrations in tissue and blood in women with breast cancer. The STS enzyme has also been shown to catalyse the formation of dehydroepiandrosterone (DHEA) from DHEA-sulfate (DHEAS). This is important since DHEA can be converted to 5-androstene-3β,17β-diol, which has been shown to possess weak estrogenic properties, however, due to the high concentration of this steroid, it is able to stimulate the growth of breast cancer cells in vitro and in vivo. Considerable progress has been made in recent years in the development of a number of potent E1STS inhibitors, as such both steroidal and non-steroidal compounds have been considered and a number of highly potent inhibitors have been produced and evaluated against what is now considered a crucial enzyme in the fight against hormone-dependent breast cancer. The review therefore summarises the work that has been undertaken todate.
Export Options
About this article
Cite this article as:
Aidoo-Gyamfi Kwabina, Cartledge Tim, Shah Kruti and Ahmed Sabbir, Estrone Sulfatase and Its Inhibitors, Anti-Cancer Agents in Medicinal Chemistry 2009; 9 (6) . https://dx.doi.org/10.2174/187152009788679985
DOI https://dx.doi.org/10.2174/187152009788679985 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Historical Spice as a Future Drug: Therapeutic Potential of Piperlongumine
Current Pharmaceutical Design Meet Our Executive Editor
Current Traditional Medicine Editorial (Thematic Issue: Targeting Mammalian Spermatogenesis: A Matter of Support)
Current Molecular Pharmacology Novel Kynurenic Acid Analogues in the Treatment of Migraine and Neurodegenerative Disorders: Preclinical Studies and Pharmaceutical Design
Current Pharmaceutical Design Evaluation of a New <sup>99m</sup>Tc-labeled GnRH Analogue as a Possible Imaging Agent for Prostate Cancer Detection
Anti-Cancer Agents in Medicinal Chemistry Global View on Rare Diseases: A Mini Review
Current Medicinal Chemistry Discovery of MINC1, a GTPase-Activating Protein Small Molecule Inhibitor, Targeting MgcRacGAP
Combinatorial Chemistry & High Throughput Screening Construction, Expression and Functional Characterization of the β-Lactamase with αv Integrin Ligands
Protein & Peptide Letters circEPSTI1 Acts as a ceRNA to Regulate the Progression of Osteosarcoma
Current Cancer Drug Targets The S100A8 and S100A9 Proteins are Attractive Targets to Modulate Inflammation
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Serum S-100B Protein as A Biochemical Marker of Brain Injury: A Review of Current Concepts
Current Medicinal Chemistry Induction of Apoptosis by Nano-Synthesized Complexes of H2L and its Cu(II) Complex in Human Hepatocellular Carcinoma Cells
Anti-Cancer Agents in Medicinal Chemistry Medicinal Applications of Cannabinoids Extracted from Cannabis sativa (L.): A New Route in the Fight Against COVID-19?
Current Pharmaceutical Design SCAN-Toolbox: Structural COBRA Add-oN (SCAN) for Analysing Large Metabolic Networks
Current Bioinformatics Antioxidant, Pro-Oxidant and Other Biological Activities of Sesquiterpenes
Current Topics in Medicinal Chemistry miRNAs Highlights in Stem and Cancer Cells
Mini-Reviews in Medicinal Chemistry SCYL1-BP1 Affects Cell Cycle Arrest in Human Hepatocellular Carcinoma Cells via Cyclin F and RRM2
Anti-Cancer Agents in Medicinal Chemistry Anti-cancer Nitrogen-Containing Heterocyclic Compounds
Current Organic Chemistry Elasticity Imaging via MRI: Basics, Overcoming the Waveguide Limit, and Clinical Liver Results
Current Medical Imaging Natural Compounds with Proteasome Inhibitory Activity for Cancer Prevention and Treatment
Current Protein & Peptide Science