HDAC6 inhibitors sensitize resistant t(11;14) multiple myeloma cells to a combination of bortezomib and BH3 mimetics.

Not available.

Antileukemic potential of methylated indolequinone MAC681 through immunogenic necroptosis and PARP1 degradation.

Background: Despite advancements in chronic myeloid leukemia (CML) therapy with tyrosine kinase inhibitors (TKIs), resistance and intolerance remain significant challenges. Leukemia stem cells (LSCs) and TKI-resistant cells rely on altered mitochondrial metabolism and oxidative phosphorylation. Targeting rewired energy metabolism and inducing non-apoptotic cell death, along with the release of damage-associated molecular patterns (DAMPs), can enhance therapeutic strategies and immunogenic therapies against CML and prevent the emergence of TKI-resistant cells and LSC persistence.

ATP1A1/BCL2L1 predicts the response of myelomonocytic and monocytic acute myeloid leukemia to cardiac glycosides.

Myelomonocytic and monocytic acute myeloid leukemia (AML) subtypes are intrinsically resistant to venetoclax-based regimens. Identifying targetable vulnerabilities would limit resistance and relapse. We previously documented the synergism of venetoclax and cardiac glycoside (CG) combination in AML.

Enhancing personalized immune checkpoint therapy by immune archetyping and pharmacological targeting.

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 predictive response markers.

Marine Natural Products as Anticancer Agents 2.0.

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

Marine Polyether Phycotoxin Palytoxin Induces Apoptotic Cell Death via Mcl-1 and Bcl-2 Downregulation.

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 and did not create systemic toxicity in zebrafish, we confirmed excellent differential toxicity.

Apoptotic cell death in disease-Current understanding of the NCCD 2023.

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 etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions.

Discovery of Sulforaphane as an Inducer of Ferroptosis in U-937 Leukemia Cells: Expanding Its Anticancer Potential.

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.

Marine Natural Products as Anticancer Agents.

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

Phytochemical Screening and Antioxidant and Cytotoxic Effects of .

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 and methanol ) and stem (dichloromethane and methanol ) bark extracts of were assessed on chronic K562 and acute U937 myeloid leukemia cancer cells using trypan blue, Hoechst, and MitoTracker Red staining methods.

Anticancer properties of indole derivatives as IsoCombretastatin A-4 analogues.

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 sub-nanomolar level of cytotoxicity (IC < 1 nM) against 9 human cancer cell lines.

Anti-Leukemic Properties of Aplysinopsin Derivative EE-84 Alone and Combined to BH3 Mimetic A-1210477.

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 of newly synthesized aplysinopsin analogs on myelogenous leukemia cell lines and zebrafish toxicity tests, as well as analysis of differential toxicity in noncancerous RPMI 1788 cells and PBMCs, we identified EE-84 as a promising novel drug candidate against chronic myeloid leukemia.

Assessment of Mitochondrial Cell Metabolism by Respiratory Chain Electron Flow Assays.

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 organelle maintaining optimal cellular energy levels.

Bioactive Bromotyrosine Derivatives from the Pacific Marine Sponge (Pulitzer-Finali, 1982).

Chemical investigation of the South-Pacific marine sponge led to the isolation of eight new bromotyrosine metabolites named subereins 1-8 (-) along with twelve known co-isolated congeners. The detailed configuration determination of the first representative major compound of this family 11--fistularin-3 (11,17) () is described. Their chemical characterization was achieved by HRMS and integrated 1D and 2D NMR (nuclear magnetic resonance) spectroscopic studies and extensive comparison with literature data.

Susceptibility of multiple myeloma to B-cell lymphoma 2 family inhibitors.

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 MM patients, this cancer remains currently incurable; due in part to the emergence of resistant clones, highlighting the unmet need for innovative therapeutic approaches. Accumulating evidence suggests that the survival of MM molecular subgroups depends on the expression profiles of specific subsets of anti-apoptotic B-cell lymphoma (BCL)-2 family members.

Bioactivity of natural biflavonoids in metabolism-related disease and cancer therapies.

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.

Asciminib Mitigates DNA Damage Stress Signaling Induced by Cyclophosphamide in the Ovary.

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.