Michael Schnekenburger

4-Hydroxybenzoic acid derivatives as HDAC6-specific inhibitors modulating microtubular structure and HSP90a chaperone ac...

Published in Biochemical Pharmacology in Jan 02, 2016

Histone deacetylase (HDAC)6 is a unique isoenzyme targeting specific substrates including a-tubulin and heat shock protein (HSP)90. HDAC6 is involved in protein trafficking and degradation, cell shape and migration. Deregulation of HDAC6 activity is associated with a variety of diseases including cancer leading to a growing interest for developing ...

Antiproliferative and proapoptotic activities of 4-hydroxybenzoic acid-based inhibitors of histone deacetylases

Published in Cancer Letters

Histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate cellular processes by modifying the acetylation status of many proteins. Pathologically altered HDAC activity contributes to cancer development and thus characterization of novel acetylation modulators is important for future anti-cancer therapies. In this study, we identif...

The DNA hypomethylating agent, 5-aza-2′-deoxycytidine, enhances tumor cell invasion through a transcription-dependent ...

Published in Molecular Carcinogenesis

In diseases such as cancer, cells need to degrade the extracellular matrix (ECM) and therefore require high protease levels. Thus, aberrant tissue degradation is associated to matrix metalloproteinases (MMPs) overexpression resulting from different mechanisms including epigenetic events. One of the most characterized epigenetic mechanisms is DNA me...

UNBS1450, a steroid cardiac glycoside inducing apoptotic cell death in human leukemia cells

Published in Biochemical Pharmacology

Cardiac steroids are used to treat various diseases including congestive heart failure and cancer. The aim of this study was to investigate the anti-leukemic activity of UNBS1450, a hemi-synthetic cardenolide belonging to the cardiac steroid glycoside family. Here, we report that, at low nanomolar concentrations, UNBS1450 induces apoptotic cell dea...

Epigenetically induced changes in nuclear textural patterns and gelatinase expression in human fibrosarcoma cells

Published in Cell Proliferation

Chromatin texture patterns of tumour cell nuclei can serve as cancer biomarkers, either to define diagnostic classifications or to obtain relevant prognostic information, in a large number of human tumours. Epigenetic mechanisms, mainly DNA methylation and histone post-translational modification, have been shown to influence chromatin packing state...

DNA demethylation increases sensitivity of neuroblastoma cells to chemotherapeutic drugs

Published in Biochemical Pharmacology

Neuroblastoma is a common embryonal malignancy in which high-stage cases have a poor prognosis, often associated with resistance to chemotherapeutic drugs. DNA methylation alterations are frequent in neuroblastoma and can modulate sensitivity to chemotherapeutic drugs in other cancers, suggesting that manipulation of epigenetic modifications could ...

Tumor necrosis factor alpha inhibits aclacinomycin A-induced erythroid differentiation of K562 cells via GATA-1

Published in Cancer Letters

Up-regulation of tumor necrosis factor alpha (TNFalpha) is linked to solid tumors as well as to hematologic disorders including different forms of anemia and multiple myeloma. This cytokine was shown to contribute to inhibition of erythroid maturation mechanisms which are characterized by the expression of specific genes regulated by GATA-1 and NF-...

Transcriptional and post-transcriptional regulation of glutathione S-transferase P1 expression during butyric acid-induc...

Published in Leukemia Research

Over-expression of glutathione S-transferase P1 is related to chemotherapeutic drug resistance as well as to differentiation of human erythroleukemia cells. In opposition to previously described differentiating inducers which enhance the GST-resistance phenotype, time- and concentration-dependent activation of both erythroid and megakaryocytic diff...

Valproic acid perturbs hematopoietic homeostasis by inhibition of erythroid differentiation and activation of the myelo-...

Published in Biochemical Pharmacology

As a histone deacetylase inhibitor, valproic acid (VPA) is a candidate for anticancer therapy. Besides, VPA exhibits various mechanisms of action and its effects on the molecular basis of hematopoiesis remain unclear. To study the effects of VPA on the hematopoietic system, we performed microarray analysis using K562 cells treated with 1mM VPA over...

Chemopreventive and therapeutic effects of curcumin

Published in Cancer Letters

Chemoprevention is a promising anti-cancer approach with reduced secondary effects in comparison to classical chemotherapy. Curcumin, one of the most studied chemopreventive agents, is a natural compound extracted from Curcuma longa L. that allows suppression, retardation or inversion of carcinogenesis. Curcumin is also described as an anti-tumoral...

GATA-1: Friends, Brothers, and Coworkers

Published in Annals of the New York Academy of Sciences

GATA-1 is the founding member of the GATA family of transcription factors. GATA-1 and GATA family member GATA-2 are expressed in erythroid and megakaryocytic lineages, in which they play a crucial role in cell maturation and differentiation. GATA-1 regulates the transcription of many specific and nonspecific erythroid genes by binding to DNA at the...

Chromium Cross-Links Histone Deacetylase 1-DNA Methyltransferase 1 Complexes to Chromatin, Inhibiting Histone-Remodeling...

Published in Molecular and Cellular Biology

An Introduction to the Molecular Mechanisms of Apoptosis

Published in Annals of the New York Academy of Sciences

Apoptosis is a type of cell death that has been observed and studied for more than a century. The process of apoptosis was described as "programmed cell death" in 1964, and the term apoptosis, from a Greek word meaning "to fall away from" and describing the fall of dead leaves from trees in autumn, was only coined in 1972. During the last 30 years,...

Expression of glutathione S-transferase P1-1 in differentiating K562: role of GATA-1

Published in Biochemical and Biophysical Research Communications

Glutathione S-transferase P1-1 (GSTP1-1) conjugates glutathione to electrophilic compounds and its expression is correlated to chemotherapeutic drug resistance. Results show that GSTP1-1 mRNA as well as protein expressions are increased during Aclarubicin (Acla)- and Doxorubicin (Dox)-induced erythroid differentiation of human K562 cells. In contra...

Sustained exposure to the DNA demethylating agent, 2′-deoxy-5-azacytidine, leads to apoptotic cell death in chronic my...

Published in Biochemical Pharmacology

In addition to its demethylating properties, 2'-deoxy-5-azacytidine (DAC) induces cell cycle arrest, differentiation, cell sensitization to chemotherapy, and cell death. However, the mechanisms by which DAC induces antiproliferation via these processes and how they are interconnected remain unclear. In this study, we found that a clinically relevan...

Plant-derived epigenetic modulators for cancer treatment and prevention

Published in Biotechnology Advances

Carcinogenesis is a complex and multistep process that involves the accumulation of successive transformational events driven by genetic mutations and epigenetic alterations that affect major cellular processes and pathways such as proliferation, differentiation, invasion and survival. Massive deregulation of all components of the epigenetic machin...

Chromatin-modifying agents in anti-cancer therapy

Published in Biochimie

Epigenetic alterations are involved in every step of carcinogenesis. The development of chromatin- modifying agents (CMAs) has provided the ability to fight cancer by reversing these alterations. Currently, four CMAs have been approved for cancer treatment; two DNA demethylating agents and two deacetylase inhibitors. A number of promising CMAs are ...

Novel inhibitors of human histone deacetylases: Design, synthesis and bioactivity of 3-alkenoylcoumarines

Published in Bioorganic & Medicinal Chemistry Letters

Histone deacetylases (HDACs) are well-established, promising targets for anticancer therapy due to their critical role in cancer development. Accordingly, an increasing number of HDAC inhibitors displaying cytotoxic effects against cancer cells have been reported. Among them, a large panel of chemical structures was described including coumarin-con...