Molecular and Biochemical Analysis of the Estrogenic and Proliferative Properties of Vitamin E Compounds

Frontiers in Oncology
Farid KhalloukiSandrine Silvente-Poirot

Abstract

Tocols are vitamin E compounds that include tocopherols (TPs) and tocotrienols (TTs). These lipophilic compounds are phenolic antioxidants and are reportedly able to modulate estrogen receptor β (ERβ). We investigated the molecular determinants that control their estrogenicity and effects on the proliferation of breast cancer cells. Docking experiments highlighted the importance of the tocol phenolic groups for their interaction with the ERs. Binding experiments confirmed that they directly interact with both ERα and ERβ with their isoforms showing potencies in the following order: δ-tocols > γ-tocols > α-tocols. We also found that tocols activated the transcription of an estrogen-responsive reporter gene that had been stably transfected into cells expressing either ERα or ERβ. The role of the phenolic group in tocol-ER interaction was further established using δ-tocopherylquinone, the oxidized form of δ-TP, which had no ER affinity and did not induce ER-dependent transcriptional modulation. Tocol activity also required the AF1 transactivation domain of ER. We found that both δ-TP and δ-TT stimulated the expression of endogenous ER-dependent genes. However, whereas δ-TP induced the proliferation of ER-positive breast cancer cel...Continue Reading

References

Jul 4, 1990·Journal of the National Cancer Institute·P SkehanM R Boyd
Aug 1, 1993·Journal of the American College of Nutrition·J E MansonC H Hennekens
Jun 7, 1996·The Journal of Biological Chemistry·U GundimedaR Gopalakrishna
Mar 1, 1997·The American Journal of Clinical Nutrition·C KiyoseO Igarashi
May 1, 1997·The Journal of Nutrition·L HeC E Elson
Oct 24, 1997·Nature·A M BrzozowskiM Carlquist
Mar 16, 2001·Structure·A C PikeM Carlquist
May 23, 2001·Experimental Biology and Medicine·N KaulI Jialal
Jun 4, 2002·Nature Reviews. Neuroscience·Christian Behl
Nov 18, 2003·The Journal of Pharmacology and Experimental Therapeutics·Philippe de MedinaMarc Poirot
Jun 4, 2004·The Journal of Biological Chemistry·Blandine KedjouarMarc Poirot
Dec 8, 2004·Current Medicinal Chemistry. Anti-cancer Agents·Philippe de MédinaMarc Poirot
Feb 22, 2005·International Journal of Cancer. Journal International Du Cancer·Yoshihisa YanoTomohiro Yano
Mar 17, 2005·JAMA : the Journal of the American Medical Association·Eva LonnUNKNOWN HOPE and HOPE-TOO Trial Investigators
Sep 17, 2005·CA: a Cancer Journal for Clinicians·Gabriella M D'Andrea
Mar 1, 2006·Molecular Cancer Therapeutics·Sreenivasa DonapatyMokenge P Malafa
Mar 3, 2006·The Journal of Clinical Investigation·Bonnie J Deroo, Kenneth S Korach
Mar 24, 2006·Biochemical Pharmacology·Aurélie EscandePatrick Balaguer
Jul 7, 2007·Physiological Reviews·Nina HeldringJan-Ake Gustafsson
May 13, 2008·The Journal of Surgical Research·Elizabeth A PeraltaGary L Dunnington
Aug 19, 2008·Toxicology and Applied Pharmacology·José-Manuel Molina-MolinaPatrick Balaguer
Dec 11, 2008·JAMA : the Journal of the American Medical Association·Scott M LippmanCharles A Coltman
Jun 6, 2009·American Journal of Physiology. Endocrinology and Metabolism·Raffaella ComitatoFabio Virgili
Aug 11, 2010·Biochemical Pharmacology·Bharat B AggarwalRamaswamy Kannappan
Aug 13, 2010·Molecular Pharmacology·Philippe de MedinaMarc Poirot
May 23, 2012·Biochimie·Marc Poirot, Sandrine Silvente-Poirot
Aug 25, 2012·Current Opinion in Pharmacology·Sandrine Silvente-Poirot, Marc Poirot
Oct 16, 2012·Current Opinion in Pharmacology·Marc PoirotRalph R Weichselbaum

❮ Previous
Next ❯

Citations

Jan 18, 2019·Recent Patents on Anti-cancer Drug Discovery·Fabrizio FontanaPatrizia Limonta
Apr 25, 2019·European Journal of Nutrition·Constantina ConstantinouDimitrios Kanakis
Aug 6, 2020·International Journal of Molecular Sciences·Michał CiebieraAyman Al-Hendy

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
FCS
biopsies

Software Mentioned

Discover
GraphPad
Prism
GraphPad prism
Insight
Insight II
Search

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.