Mitochondrial-mediated apoptosis as a therapeutic target for FNC (2′-deoxy-2′-b-fluoro-4′-azidocytidine)-induced inhibition of Dalton’s lymphoma growth and proliferation DOI Creative Commons
Naveen Kumar, Sanjeev Kumar, Alok Shukla

et al.

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 22, 2024

Abstract Purpose T-cell lymphomas, refer to a diverse set of lymphomas that originate from T-cells, type white blood cell, with limited treatment options. This investigation aimed assess the efficacy and mechanism novel fluorinated nucleoside analogue (FNA), 2′-deoxy-2′-β-fluoro-4′-azidocytidine (FNC), against lymphoma using Dalton’s (DL)-bearing mice as model. Methods Balb/c transplanted DL tumor model received FNC study therapeutic lymphoma. Behavioral monitoring, physiological measurements, various analyses were conducted evaluate effects for mechanistic investigations. Results The results indicated prevented DL-altered behavior parameters, weight gain alteration in organ structure, hematological liver enzyme levels. Moreover, restored structures, attenuated angiogenesis, reduced cell viability proliferation through apoptosis. revealed diminished MMP levels, induced apoptosis ROS induction, activated mitochondrial-mediated pathways leading increase mean survival time mice. These findings suggest has potential mitigating DL-induced adverse effects. Conclusion represents an efficient targeted strategy FNC’s proficient ability induce generation reduction makes it promising candidate developing newer more effective anticancer therapies. Continued research could unveil role designing better approach NHL.

Language: Английский

Carbonic Anhydrase Inhibitors Targeting Metabolism and Tumor Microenvironment DOI Creative Commons
Andrea Angeli, Fabrizio Carta, Alessio Nocentini

et al.

Metabolites, Journal Year: 2020, Volume and Issue: 10(10), P. 412 - 412

Published: Oct. 14, 2020

The tumor microenvironment is crucial for the growth of cancer cells, triggering particular biochemical and physiological changes, which frequently influence outcome anticancer therapies. rationale behind many these phenomena resides in activation transcription factors such as hypoxia-inducible factor 1 2 (HIF-1/2). In turn, HIF pathway activates a number genes including those involved glucose metabolism, angiogenesis, pH regulation. Several carbonic anhydrase (CA, EC 4.2.1.1) isoforms, CA IX XII, actively participate processes were validated antitumor/antimetastatic drug targets. Here, we review field inhibitors (CAIs), selectively inhibit cancer-associated isoforms. Particular focus was on identification lead compounds various inhibitor classes, measurement inhibitory on-/off-target effects. addition, preclinical data that resulted SLC-0111, sulfonamide Phase Ib/II clinical trials treatment hypoxic, advanced solid tumors, are detailed.

Language: Английский

Citations

143
Carboranes as unique pharmacophores in antitumor medicinal chemistry DOI Creative Commons
Yu Chen, Fukuan Du,

Liyao Tang

et al.

Molecular Therapy — Oncolytics, Journal Year: 2022, Volume and Issue: 24, P. 400 - 416

Published: Jan. 10, 2022

Carborane is a carbon-boron molecular cluster that can be viewed as 3D analog of benzene. It features special physical and chemical properties, thus has the potential to serve new type pharmacophore for drug design discovery. Based on relative positions two cage carbons, icosahedral closo-carboranes classified into three isomers, ortho-carborane (o-carborane, 1,2-C2B10H12), meta-carborane (m-carborane, 1,7-C2B10H12), para-carborane (p-carborane, 1,12-C2B10H12), all them deboronated generate their nido- forms. Cage compound carborane its derivatives have been demonstrated useful entities in antitumor medicinal chemistry. The applications carboranes field research mainly include boron neutron capture therapy (BNCT), BNCT/photodynamic dual sensitizers, anticancer ligands. This review summarizes progress achieved up October 2021, with particular emphasis signaling transduction pathways, structures, mechanistic considerations using carboranes.

Language: Английский

Citations

73
A review of biological targets and therapeutic approaches in the management of triple-negative breast cancer DOI Creative Commons
Hitesh Kumar, Neha Gupta, Rupshee Jain

et al.

Journal of Advanced Research, Journal Year: 2023, Volume and Issue: 54, P. 271 - 292

Published: Feb. 14, 2023

Triple-negative breast cancer (TNBC) is a heterogeneous, aggressive phenotype of with associated chemoresistance. The development chemo- or radioresistance could be attributed to diverse tumor microenvironments, overexpression membrane proteins (transporters), epigenetic changes, and alteration the cell signaling pathways/genes stem cells (CSCs). Due heterogeneous nature TNBC, therapeutic response existing modalities offers limited scope thus results in reccurance after therapy. To establish landmark efficacy, number novel have been proposed. In addition, reversal resistance that developed during treatment may altered by employing appropriate modalities. This review aims discuss plethora investigations carried out, which will help readers understand make an choice therapy directed toward complete elimination TNBC. manuscript addresses major contributory factors from microenvironment are responsible for chemoresistance poor prognosis. cellular events molecular mechanism-based interventions explained detail. Inhibition ABC transporters, pathways CSCs, modification promising this regard. TNBC progression, invasion, metastasis recurrence can also inhibited blocking multiple pathways, targeting specific receptors/epigenetic targets, disrupting bioenergetics generating reactive oxygen species (ROS).

Language: Английский

Citations

60
A Strategy of Fenton Reaction Cycloacceleration for High‐Performance Ferroptosis Therapy Initiated by Tumor Microenvironment Remodeling DOI
Lin Huang, Jie Feng,

Jiaoyang Zhu

et al.

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(18)

Published: March 9, 2023

Abstract The emerging tumor ferroptosis therapy confronts impediments of the microenvironment (TME) with weak intrinsic acidity, inadequate endogenous H 2 O , and a powerful intracellular redox balance system that eliminates toxic reactive oxygen species (ROS). Herein, strategy Fenton reaction cycloacceleration initiated by remodeling TME for magnetic resonance imaging (MRI)‐guided high‐performance tumors is proposed. synthesized nanocomplex exhibits enhanced accumulation at carbonic anhydrase IX (CAIX)‐positive based on CAIX‐mediated active targeting, increased acidification via inhibition CAIX 4‐(2‐aminoethyl) benzene sulfonamide (ABS) (remodeling TME). This accumulated + abundant glutathione in synergistically trigger biodegradation to release loaded cuprous oxide nanodots (CON), β ‐lapachon (LAP), Fe 3+ gallic acid‐ferric ions coordination networks (GF). Fenton‐like reactions are cycloaccelerated catalytic loop Fe‐Cu, LAP‐triggered nicotinamide adenine dinucleotide phosphate quinone oxidoreductase1‐mediated cycle, generating robust ROS plenitudinous lipid peroxides cells. detached GF network has improved relaxivities response TME. Therefore, promising MRI‐guided tumors.

Language: Английский

Citations

47
Insights into tumor-derived exosome inhibition in cancer therapy DOI
Ziwei Tang, Cheng Chen, Chen Zhou

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 285, P. 117278 - 117278

Published: Jan. 13, 2025

Language: Английский

Citations

3
Reconsidering anion inhibitors in the general context of drug design studies of modulators of activity of the classical enzyme carbonic anhydrase DOI Creative Commons
Alessio Nocentini, Andrea Angeli, Fabrizio Carta

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2021, Volume and Issue: 36(1), P. 561 - 580

Published: Jan. 1, 2021

Inorganic anions inhibit the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) generally by coordinating to active site metal ion. Cyanate was reported as a non-coordinating CA inhibitor but those erroneous results were subsequently corrected another group. We review anion inhibitors (CAIs) in more general context of drug design studies and discovery large number classes inhibition mechanisms, including zinc binders (sulphonamides isosteres, dithiocabamates thiols, selenols, benzoxaboroles, ninhydrins, etc.); anchoring zinc-coordinated water molecule (phenols, polyamines, sulfocoumarins, thioxocoumarins, catechols); CAIs occluding entrance (coumarins derivatives, lacosamide), well compounds that bind outside site. All these new chemotypes integrated with procedure for obtaining isoform-selective (the tail approach) has resulted, through guidance rigorous X-ray crystallography experiments, development highly selective all human isoforms many pharmacological applications.

Language: Английский

Citations

104
HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells DOI Creative Commons
Shen‐Han Lee, Monika Golinska, John R. Griffiths

et al.

Cells, Journal Year: 2021, Volume and Issue: 10(9), P. 2371 - 2371

Published: Sept. 9, 2021

In solid tumours, cancer cells exist within hypoxic microenvironments, and their metabolic adaptation to this hypoxia is driven by HIF-1 transcription factor, which overexpressed in a broad range of human cancers. HIF inhibitors are under pre-clinical investigation clinical trials, but there evidence that can adapt metabolically inhibition, would provide potential route for drug resistance. Here, we review accumulating such adaptions carbohydrate creatine metabolism other HIF-1-independent mechanisms might allow cancers survive despite anti-HIF-1 therapy. These include pathways glucose, glutamine, lipid metabolism; epigenetic mechanisms; post-translational protein modifications; spatial reorganization enzymes; signalling as Myc, PI3K-Akt, 2-hyxdroxyglutarate AMP-activated kinase (AMPK); activation the HIF-2 pathway. All these should be investigated future work on bypass principle, agents targeted toward HIF-1β rather than HIF-1α advantageous, both require activation. However, also aryl hydrocarbon nuclear transporter (ARNT), has functions many tissues, so off-target effects expected. general, therapy inhibition will need careful attention resistance mechanisms.

Language: Английский

Citations

99
Recent Progress in Magnetically Actuated Microrobots for Targeted Delivery of Therapeutic Agents DOI
Junhee Choi, Junsun Hwang,

Jin‐young Kim

et al.

Advanced Healthcare Materials, Journal Year: 2020, Volume and Issue: 10(6)

Published: Dec. 16, 2020

Abstract Therapeutic agents, such as drugs and cells, play an essential role in virtually every treatment of injury, illness, or disease. However, the conventional practices drug delivery often result undesirable side effects caused by overdose off‐target delivery. In case cell delivery, survival rate transplanted cells is extremely low difficulties with administration route remain a problem. Recently, magnetically actuated microrobots have started offering unique opportunities targeted therapeutic due to their tiny size ability access hard‐to‐reach lesions minimally invasive manner; considerable advances this regard been made over past decade. Here, recent progress microrobots, developed for drug/cell presented, focus on design features mechanisms controlled release. Additionally, practical challenges faced future research directions toward swift bench‐to‐bedside translation are addressed.

Language: Английский

Citations

97
Carbonic anhydrase inhibitors: an update on experimental agents for the treatment and imaging of hypoxic tumors DOI
Claudiu T. Supuran

Expert Opinion on Investigational Drugs, Journal Year: 2021, Volume and Issue: 30(12), P. 1197 - 1208

Published: Dec. 2, 2021

Hypoxic tumors, unlike normal tissues, overexpress proteins involved in oxygen sensing, metabolism, pH regulation, angiogenesis, immunological response, and other survival mechanisms, which are under investigation as antitumor drug targets.Carbonic anhydrase (CA) isoforms CA IX XII among these validated antitumor/antimetastatic targets, with several of their inhibitors undergoing preclinical or clinical-stage investigations. Alone combination chemotherapeutic agents radiotherapy, IX/XII inhibitors, such SLC-0111, SLC-149, S4, 6A10, etc., were shown to inhibit the growth primary tumor, metastases, invasiveness many tumor types, being also amenable for development imaging agents.SLC-0111 is most investigated agent, Phase Ib/II clinical trials. In addition its interference extracellular acidifications, it has been promote ferroptosis cancer cells, another mechanism this compound entire class. A large number sulfonamide non-sulfonamide have developed using SLC-0111 lead last three years, together hybrid incorporating anticancer chemotypes, including cytotoxins, telomerase, thioredoxin P-glycoprotein adenosine A2A receptor antagonists, pyrophosphatase/phosphodiesterase-3 antimetabolites. All them showed significant activity.

Language: Английский

Citations

73
Metabolic tricks of cancer cells DOI
Kateřina Hönigová, Jiří Navrátil, Barbora Peltanová

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2022, Volume and Issue: 1877(3), P. 188705 - 188705

Published: March 8, 2022

Language: Английский

Citations

53