Antimyeloma Potential of Caffeic Acid Phenethyl Ester and Its Analogues through Sp1 Mediated Downregulation of IKZF1-IRF4-MYC Axis.

Journal of Natural Products
Alli MurugesanTony Reiman

Abstract

Caffeic acid phenethyl ester (CAPE, 2), a natural compound from propolis, is a well-documented antitumor agent with nuclear factor kappa B (NF-κB) inhibitory activity. Key transcription factors regulated by NF-κB, namely, interferon regulatory factor-4 (IRF4) and octameric binding protein-2 (OCT2), are implicated in the tumorigenesis of multiple myeloma (MM), an incurable bone marrow cancer. Adverse effects and resistance to current chemotherapeutics pose a great challenge for MM treatment. Hence, the structure-activity relationships of CAPE (2) and 21 of its analogues were evaluated for their antimyeloma potential. Preclinical evaluation revealed that CAPE (2) and the 3-phenylpropyl (4), 2,5-dihydroxycinnamic acid 3-phenylpropyl ester (17), and 3,4-dihydroxycinnamic ether (22) analogues inhibited human myeloma cell growth. Analogue 4 surpassed CAPE (2) and lenalidomide in showing strong apoptotic effects with a remarkable decrease in IRF4 levels. The analogue 17 exhibited the most potent anti-MM activity. The downregulation of specificity protein 1 (Sp1) and the IKZF1-IRF4-MYC axis by CAPE (2) analogues 4 and 17 revealed their novel mechanism of action. The analogues showed no adverse cytotoxic effects on normal human cells an...Continue Reading

References

Aug 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·K NatarajanB B Aggarwal
Nov 5, 1997·Nature Genetics·S IidaR Dalla-Favera
Nov 20, 1997·The Journal of Biological Chemistry·H H BendallE M Oltz
Jun 29, 1999·Cold Spring Harbor Symposia on Quantitative Biology·A M NäärR Tjian
Nov 24, 1999·The New England Journal of Medicine·S SinghalB Barlogie
Nov 26, 1999·Gene·G Suske
Dec 1, 2001·Expert Opinion on Biological Therapy·J B MarriottA G Dalgleish
May 31, 2002·Journal of Medicinal Chemistry·Daniel F VeberKenneth D Kopple
Jan 17, 2003·Mayo Clinic Proceedings·Robert A KylePhilip R Greipp
Sep 13, 2003·Blood·Bart BarlogieJohn Crowley
Jan 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Manuel A SepulvedaBarbara K Birshtein
Oct 11, 2005·Mayo Clinic Proceedings·S Vincent Rajkumar, Robert A Kyle
Jun 13, 2006·Nature Immunology·Ulf KleinRiccardo Dalla-Favera
Jun 24, 2008·Nature·Arthur L ShafferLouis M Staudt
Sep 30, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Paul G RichardsonKenneth C Anderson
Nov 7, 2009·Evidence-based Complementary and Alternative Medicine : ECAM·Ewelina SzliszkaWojciech Krol
Mar 13, 2010·Science·Takumi ItoHiroshi Handa
Aug 23, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mariateresa FulcinitiNikhil C Munshi
Jul 19, 2012·Blood·Toril HolienAnders Sundan
Jun 6, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Viviane Cristina ToretiYong Kun Park
Sep 17, 2014·American Journal of Hematology·S Vincent Rajkumar
Oct 15, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Pengxuan ZhangJin-Ao Duan
Feb 28, 2015·Journal of Dietary Supplements·Seema Patel
Feb 28, 2015·Blood Cancer Journal·P J Hengeveld, M J Kersten
Jul 3, 2015·Experimental and Therapeutic Medicine·Ferah ArmutcuFatime Filiz Turan
Jul 18, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Annie-Pier BeauregardGilles A Robichaud
Nov 23, 2018·Investigational New Drugs·Elizabeth Hernandez MarinXinyu Wang

❮ Previous
Next ❯

Citations

Jul 11, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Sepideh MirzaeiGautam Sethi

❮ Previous
Next ❯

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.

© 2021 Meta ULC. All rights reserved