Marc F Diederich

Seoul National University | SNU · College of Pharmacy

Resistance to apoptotic cell death1 owing to overexpression of anti-apoptotic Bcl-2 family proteins including Bcl-2, Bcl-xL or Mcl-1 is considered an interesting druggable target for the treatment of hematological malignancies including acute myeloid leukemia. In fact, BH3 mimetics2 like ABT-199 (venetoclax)3 reverse the inhibitory function of anti...

Elevated tumor necrosis factor (TNF) α serum levels constitute an adverse prognostic factor for the survival of acute myeloid leukemia (AML) patients. TNF is produced by various immune effectors and directly or indirectly acts as a pro-proliferative autocrine tumor growth factor. TNF -controlled regulatory mechanisms, especially by long non-coding...

B cell lymphoma 2 (BCL2) homology domain 3 (BH3) mimetics are targeted therapeutic agents that allow response prediction and patient stratification. BH3 mimetics are prototypical activators of the mitochondrial death program in cancer. They emerged as important modulators of cellular mechanisms contributing to poor therapeutic responses, including...

Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer and infectious diseases. Nevertheless, natural products also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization, which contributed to a declin...

Elevated levels of the pro-inflammatory cytokine tumor necrosis factor-α (TNFα) inhibit erythropoiesis and cause anemia in patients with cancer and chronic inflammatory diseases. TNFα is also a potent activator of the sphingomyelinase (SMase)/ ceramide pathway leading to ceramide synthesis and regulating cell differentiation, proliferation, apoptos...

Immune checkpoint inhibitors (ICIs) are an expanding class of immunotherapeutic agents with the potential to cure cancer. Despite the outstanding clinical response in patient subsets, most individuals become refractory or develop resistance. Patient stratification and personalized immunotherapies are limited by the absence of pre- dictive response...

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiolo...

Global cancer incidence and death are expected to increase to 28 [...]

Palytoxin is considered one of the most potent biotoxins. As palytoxin-induced cancer cell death mechanisms remain to be elucidated, we investigated this effect on various leukemia and solid tumor cell lines at low picomolar concentrations. As palytoxin did not affect the viability of peripheral blood mononuclear cells (PBMC) from healthy donors an...

In recent years, natural compounds have emerged as inducers of non-canonical cell death. The isothiocyanate sulforaphane (SFN) is a well-known natural anticancer compound with remarkable pro-apoptotic activity. Its ability to promote non-apoptotic cell-death mechanisms remains poorly investigated. This work aimed to explore the capacity of SFN to i...

Cancer remains one of the major threats to human health and one of the deadliest diseases worldwide [...]

Histone deacetylase (HDAC) 6 is a zinc-dependent enzyme of HDAC class IIb. HDAC6 is unique within the HDAC family due to a particular structure giving it unique biological functions implicated in all major cell pathways. This isoenzyme is mainly active in the cytoplasm and possesses two functional catalytic sites and an ubiquitin-binding domain. Th...

Acacia macrostachya is used in Burkina Faso folk medicine for the treatment of inflammation and cancer. The purpose of this study was to evaluate the antioxidant and cytotoxic effects of this plant. The cytotoxic effects of root (dichloromethane B1 and methanol B2) and stem (dichloromethane B3 and methanol B4) bark extracts of A. macrostachya were...

Cellular energy metabolism is regulated by complex metabolic pathways. Although anaerobic glycolysis was reported as a primary source of energy in cancer leading to a high rate of lactate production, current evidence shows that the main energy source supporting cancer cell metabolism relies on mitochondrial metabolism. Mitochondria are the key orga...

In this study, a variety of original ligands related to Combretastatin A-4 and isoCombretastatin A-4, able to inhibit the tubulin polymerization into microtubules, was designed, synthesized, and evaluated. Our lead compound 15d having a quinazoline as A-ring and a 2-substituted indole as B-ring separated by a N-methyl linker displayed a remarkable...

Call for papers: "Next-Generation Cancer Therapies based on a (R)evolution of the Biomarker Landscape", Frontiers in Pharmacology Submission is open for the Research Topic “Next-Generation Cancer Therapies based on a (R)evolution of the Biomarker Landscape” to be published in Frontiers in Pharmacology. We welcome both Original Research and Genera...

Aplysinopsins are a class of marine indole alkaloids that exhibit a wide range of biological activities. Although both the indole and N-benzyl moieties of aplysinopsins are known to possess antiproliferative activity against cancer cells, their mechanism of action remains unclear. Through in vitro and in vivo proliferation and viability screening o...

Multiple myeloma (MM) is a biologically complex hematological disorder defined by the clonal proliferation of malignant plasma cells producing excessive monoclonal immunoglobulin that interacts with components of the bone marrow microenvironment, resulting in the major clinical features of MM. Despite the development of numerous protocols to treat...

Chemical investigation of the South-Pacific marine sponge Suberea clavata led to the isola- tion of eight new bromotyrosine metabolites named subereins 1–8 (2–9) along with twelve known co-isolated congeners. The detailed configuration determination of the first representative major compound of this family 11-epi-fistularin-3 (11R,17S) (1) is descr...

Natural biflavonoids, such as amentoflavone, bilobetin, ginkgetin, isoginkgetin, taiwaniaflavone, morelloflavone, delicaflavone, hinokiflavone, and other derivatives (~40 biflavonoids), are isolated from Selaginella sp., Ginkgo biloba, Garcinia sp., and several other species of plants. They are able to exert therapeutic benefits by regulating sever...

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...

Cancer treatments can often adversely affect the quality of life of young women. One of the most relevant negative impacts is the loss of fertility. Cyclophosphamide is one of the most detrimental chemotherapeutic drugs for the ovary. Cyclophosphamide may induce the destruction of dormant follicles while promoting follicle activation and growth. He...

the PDF can be download freely on pubmed. https://pubmed.ncbi.nlm.nih.gov/33634751/

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...

Cancer treatments often have adverse effects on the quality of life for young women. One of the most relevant negative impacts is the loss of fertility. Cyclophosphamide is one of the most detrimental chemotherapeutic drugs for the ovary. Cyclophosphamide may induce the destruction of dormant follicles while promoting follicle activation and growth...

Despite the discovery of tyrosine kinase inhibitors (TKIs) for the treatment of breakpoint cluster region-Abelson (BCR-ABL)⁺ cancer types, patients with chronic myeloid leukemia (CML) treated with TKIs develop resistance and severe adverse effects. Combination treatment, especially with a histone deacetylase (HDAC) 6 inhibitor (HDAC6i), appears to...

Background: Chronic myeloid leukemia (CML) pathogenesis is mainly driven by the oncogenic breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL) fusion protein. Since BCR-ABL displays abnormal constitutive tyrosine kinase activity, therapies using tyrosine kinase inhibitors (TKis) such as imatinib represent a major bre...

By comparing imatinib-sensitive and -resistant chronic myeloid leukemia (CML) cell models, we investigated the molecular mechanisms by which tetrahydrobenzimidazole derivative TMQ0153 triggered caspase-dependent apoptosis at low concentrations accompanied by loss of mitochondrial membrane potential (MMP) and increase of cytosolic free Ca2+ levels....

Elevated levels of the pro-inflammatory cytokine tumor necrosis factor-α (TNFα) inhibit erythropoiesis and cause anemia in patients with cancer and chronic inflammatory diseases. TNFα is also a potent activator of the sphingomyelinase (SMase)/ ceramide pathway leading to ceramide synthesis and regulating cell differentiation, proliferation, apoptos...

Background: Chronic myeloid leukemia (CML) pathogenesis is mainly driven by the oncogenic breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL) fusion protein. Since BCR-ABL displays abnormal constitutive tyrosine kinase activity, therapies using tyrosine kinase inhibitors (TKis) such as imatinib represent a major br...

By comparing imatinib-sensitive and -resistant chronic myeloid leukemia (CML) cell models, we investigated the molecular mechanisms by which tetrahydrobenzimidazole derivative TMQ0153 triggered caspase-dependent apoptosis at low concentrations accompanied by loss of mitochondrial membrane potential (MMP) and increase of cytosolic free Ca²⁺ levels....

The recent advances in cancer immunotherapy confirm the crucial role of the immune system in cancer progression and treatment. Chronic inflammation and reduced immune surveillance are both features of the tumor microenvironment. Strategies aimed at reverting pro-tumor inflammation and stimulating the antitumor immune components are being actively s...

Imatinib became the standard treatment for chronic myeloid leukemia (CML) about 20 years ago, which was a major breakthrough in stabilizing the pathology and improving the quality of life of patients. However, the emergence of resistance to imatinib and other tyrosine kinase inhibitors leads researchers to characterize new therapeutic targets. Seve...

Natural compounds are known to display therapeutic potential against a variety of chronic conditions, including cancer and inflammation. The efficacy of these natural substances can be associated with numerous molecular scaffolds present in extracts of living organisms, both terrestrial and marine. Recently, investigators have identified the abilit...

Editorial on the Research Topic Molecular Mechanisms and New Therapeutic Targets in Epithelial to Mesenchymal Transition (EMT) and Fibrosis Although the term “epithelial to mesenchymal transformation” was used for the first time by Betty Hay in 1968, the earliest description of the EMT process probably dates back to drawings made by the Nobel Priz...

Treatment of acute myeloid leukemia (AML) remains inefficient due to drug resistance and relapse, particularly in patients with FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD). Marine-derived natural products have recently been used for drug development against AML. We show in this study that petromurin C, which was isolated fro...

Imatinib became the standard treatment for chronic myeloid leukemia (CML) about 20 years ago, which was a major breakthrough in stabilizing the pathology and improving the quality of life of patients. However, the emergence of resistance to imatinib and other tyrosine kinase inhibitors leads researchers to characterize new therapeutic targets. Seve...

Natural products like coumarins, chalcones, and resveratrol have inherent biological activity in several models of diseases; therefore, their natural dimeric forms are highlighted in this review and their key structural similarities, isolation and pharmacological significance is discussed. These natural products may be dimerized during their biosyn...

Chronic myeloid leukemia (CML) is a hematological disorder caused by the oncogenic BCR-ABL fusion protein in more than 90% of patients. Despite the striking improvements in the management of CML patients since the introduction of tyrosine kinase inhibitors (TKis), the appearance of TKi resistance and side effects lead to treatment failure, justifyi...

Although tyrosine kinase inhibitors (TKI) revolutionized the management of chronic myeloid leukemia (CML), resistance against TKIs and leukemia stem cell (LSC) persistence remain a clinical concern. Therefore, new therapeutic strategies combining conventional and novel therapies are urgently needed. Since telomerase is involved in oncogenesis and t...

Les rôles de l’autophagie dans le développement tumoral sont multiples et dépendent du contexte biologique [1]. D’une part, la stimulation du flux autophagique peut ralentir la croissance tumorale et provoquer la mort des cellules tumorales. D’autre part, l’autophagie contrôlée qui élimine des protéines perçues comme cytotoxiques peut dans certaine...

Biotechnology is an evolving research field that covers a broad range of topics. Here we aimed to evaluate the latest research literature, to identify prominent research themes, major contributors in terms of institutions, countries/regions, and journals. The Web of Science Core Collection online database was searched to retrieve biotechnology arti...

Premature ovarian failure and infertility are adverse effects of cancer therapies. The mechanism underlying chemotherapy-mediated depletion of the ovarian reserve remains unclear. Here, we aim to identify the signaling pathways involved in the loss of the ovarian reserve to prevent the damaging effects of chemotherapy. We evaluated the effects of c...

Garlic has been used as a medicinal food for centuries. The biological activity of garlic relies on the presence of highly reactive sulfur compounds. Widespread in vitro and in vivo studies have reported the mechanism of action of the anticancer activity of garlic-derived organosulfur compounds (OSCs) in a wide range of cancer types. Moreover, epid...

Mitochondrial respiratory states and rates MitoEAGLE Task Group

Natural coumarins and derivatives isolated from various plants or microorganisms have inherent antioxi- dant, antibacterial, antifungal, antiviral and anticancer among many biological activities. Some of these coumarins and derivatives lead to self-programmed cancer cell death (apoptosis) via different mecha- nisms, which will be discussed. The lin...

Background DNA methyltransferases (DNMTs) are epigenetic enzymes involved in embryonic development, cell differentiation, epithelial to mesenchymal transition, and control of gene expression, whose overexpression or enhanced catalytic activity has been widely reported in cancer initiation and progression. To date, two DNMT inhibitors (DNMTi), 5-aza...

Diallyl polysulfides from edible plants have been widely investigated in cancer research holding the promise of a translational application. Generally recognized as inducers of mitotic arrest and cell death, yet their activities appear broad, without specific intracellular targets. Here we suggest their potential as targeted agents and cancer types...

Epigenetics refers to the study of heritable changes in gene function that are mediated by mechanisms other than nucleotide alterations in the primary DNA sequence. These changes are achieved by methylation on cytosine bases in DNA, by post-transcriptional modifications (e.g., acetylation and methylation) on histone proteins or RNA transcripts by n...

Hydroquinone (HQ) is a phenolic metabolite of benzene, which is used as a skin whitener. Insects synthesize this natural compound as a deterrent and mushrooms as a toxin. Pro-apoptotic effects of HQ were previously documented on various cancer cell types. Here we investigated the cell-death inducing mechanisms of this compound in chronic myeloid le...

The Luxembourg meeting is the fourth meeting of the NutRedOx COST Action (CA16112), which started on 29 March 2017. [...]

Accumulating evidence shows that the anti-cancer potential of the immune response that can be activated by modulation of the immunogenicity of dying cancer cells. This regulated cell death process is called immunogenic cell death (ICD) and constitutes a new innovating anti-cancer strategy with immune-modulatory potential thanks to the release of da...

Nat­ural com­pounds act as im­munoad­ju­vants as their ther­a­peu­tic ef­fects trig­ger can­cer stress re­sponse and re­lease of dam­age-as­so­ci­ated mol­e­c­u­lar pat­terns (DAMPs). These re­ac­tions oc­cur through an in­crease in the im­muno­genic­ity of can­cer cells that un­dergo stress fol­lowed by im­muno­genic cell death (ICD). These proces...

Redox changes and generation of reactive oxygen species (ROS) are part of normal cell metabolism. While low ROS levels are implicated in cellular signaling pathways necessary for survival, higher levels play major roles in cancer development as well as cell death signaling and execution. A role for redox changes in apoptosis has been long establish...

NF-ĸB affects most aspects of cellular physiology. Deregulation of NF-ĸB signaling is associated with inflammatory diseases and cancer. In this study, we evaluated the cytotoxic and NF-ĸB inhibition potential of new spiro(lactone-cyclohexanone) compounds in two different human leukemia cell lines (U937 and K562). The anti-proliferative effects of t...

The immune system represents the major primary defense line against carcinogenesis and acts by identifying and eradicating nascent transformed cells. A growing body of evidence is indicating that aberrant epigenetic reprogramming plays a key role in tumor immune escape through: 1) impaired efficient recognition of neoplastic cells by the immune sys...

This study aims to identify bioactive anticancer and anti-trypanosome secondary metabolites from the fermentation culture of Aspergillus flocculus endophyte assisted by modern metabolomics technologies. The endophyte was isolated from the stem of the medicinal plant Markhamia platycalyx and identified using phylogenetics. Principle component analys...

A healthy ageing process is important when it is considered that one-third of the population of Europe is already over 50 years old, although there are regional variations. This proportion is likely to increase in the future, and maintenance of vitality at an older age is not only an important measure of the quality of life but also key to particip...