Hsp70 Negatively Regulates Autophagy via Governing AMPK Activation, and Dual Hsp70-Autophagy Inhibition Induces Synergetic Cell Death in NSCLC Cells DOI Open Access
Bashar A. Alhasan,

Yana A. Gladova,

Dmitry V. Sverchinsky

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 9090 - 9090

Published: Aug. 22, 2024

Proteostasis mechanisms, such as proteotoxic-stress response and autophagy, are increasingly recognized for their roles in influencing various cancer hallmarks tumorigenesis, drug resistance, recurrence. However, the precise mechanisms underlying coordination remain not fully elucidated. The aim of this study is to investigate molecular interplay between Hsp70 autophagy lung adenocarcinoma cells elucidate its impact on outcomes anticancer therapies vitro. For purpose, we utilized human A549 cell line genetically modified it by knockdown or HSF1, H1299 with overexpression Hsp70. In addition, several treatments were employed, including treatment inhibitors (VER-155008 JG-98), HSF1 activator ML-346, modulators (SAR405 Rapamycin). Using immunoblotting, found that negatively regulates directly AMPK activation, uncovering a novel regulatory mechanism Genetic chemical was associated suppression autophagy. Conversely, inhibition Hsp70, chemically, resulted upregulation AMPK-mediated We further investigated whether suppression-mediated exhibits pro-survival- pro-death-inducing effects via MTT test, colony formation, CellTiter-Glo 3D-Spheroid viability assay, Annexin/PI apoptosis assay. Our results show combined along cisplatin treatment, synergistically reduces tumor metabolic activity, growth, 2D 3D models. These cytotoxic exerted substantially potentiating apoptosis, while activating rapamycin slightly rescued from apoptosis. Therefore, our findings demonstrate represents promising therapeutic approach may disrupt capacity refractory withstand conventional NSCLC.

Language: Английский

ThePI3K/AKTsignalling pathway in inflammation, cell death and glial scar formation after traumatic spinal cord injury: Mechanisms and therapeutic opportunities DOI Creative Commons
Xuegang He, Ying Li, Bo Deng

et al.

Cell Proliferation, Journal Year: 2022, Volume and Issue: 55(9)

Published: June 26, 2022

Abstract Objects Traumatic spinal cord injury (TSCI) causes neurological dysfunction below the injured segment of cord, which significantly impacts quality life in affected patients. The phosphoinositide 3kinase/serine‐threonine kinase (PI3K/AKT) signaling pathway offers a potential therapeutic target for inhibition secondary TSCI. This review summarizes updates concerning role PI3K/AKT Materials and Methods By searching articles related to TSCI field pathway, we summarized mechanisms pathway; also discuss current future treatment methods based on pathway. Results Early apoptosis autophagy after protect body against injury; prolonged inflammatory response leads accumulation pro‐inflammatory factors excessive apoptosis, as well surrounding normal nerve cells, thus aggravating subacute stage injury. Initial glial scar formation phase is protective mechanism TSCI, limits spread damage inflammation. However, mature tissue chronic hinders axon regeneration prevents recovery function. Activation can inhibit TSCI; inhibiting this reduce scar. Conclusion has an important function Inducing activation may be one strategies

Language: Английский

Citations

160
Targeting epigenetic regulators to overcome drug resistance in cancers DOI Creative Commons
Nan Wang, Ting Ma, Bin Yu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Feb. 17, 2023

Abstract Drug resistance is mainly responsible for cancer recurrence and poor prognosis. Epigenetic regulation a heritable change in gene expressions independent of nucleotide sequence changes. As the common epigenetic mechanisms, DNA methylation, histone modification, non-coding RNA have been well studied. Increasing evidence has shown that aberrant regulations contribute to tumor resistance. Therefore, targeting regulators represents an effective strategy reverse drug In this review, we summarize roles addition, as essential factors modifications, demethylases mediate or genomic modifications. Herein, comprehensively describe functions demethylase family including lysine-specific family, Jumonji C-domain-containing arginine fully discuss their regulatory mechanisms related therapeutic strategies, small-molecule inhibitors small interfering overcome resistance, are also described.

Language: Английский

Citations

154
The mechanism of ferroptosis and its related diseases DOI Creative Commons
Shijian Feng, Dan Tang, Yichang Wang

et al.

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Oct. 16, 2023

Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation lipid peroxides, provides novel avenue for delving into intersection metabolism, oxidative stress, and disease pathology. We have witnessed mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, traumatic tissue injuries. By unraveling intricate underpinnings molecular machinery, contributors, signaling conduits, regulatory networks governing researchers aim bridge gap between intricacies this unique mode multifaceted implications health disease. In light rapidly advancing landscape ferroptosis research, we present comprehensive review aiming at extensive in origins progress human diseases. This concludes careful analysis potential treatment approaches carefully designed either inhibit or promote ferroptosis. Additionally, succinctly summarized therapeutic targets compounds that hold promise targeting within various facet underscores burgeoning possibilities manipulating as strategy. summary, enriched insights both investigators practitioners, while fostering an elevated comprehension latent translational utilities. revealing basic processes investigating possibilities, crucial resource scientists medical aiding deep understanding effects situations.

Language: Английский

Citations

62
Triptolide induces apoptosis and cytoprotective autophagy by ROS accumulation via directly targeting peroxiredoxin 2 in gastric cancer cells DOI

Pengchen Chen,

Xiaoru Zhong,

Yali Song

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 587, P. 216622 - 216622

Published: Jan. 20, 2024

Language: Английский

Citations

21
Pharmacological activities and pharmacokinetics of liquiritin: A review DOI

Junyuan Qin,

Junren Chen, Peng Fu

et al.

Journal of Ethnopharmacology, Journal Year: 2022, Volume and Issue: 293, P. 115257 - 115257

Published: April 5, 2022

Language: Английский

Citations

67
The role of interaction between autophagy and apoptosis in tumorigenesis (Review) DOI Creative Commons

Hongyan Xi,

Shuo Wang, Beibei Wang

et al.

Oncology Reports, Journal Year: 2022, Volume and Issue: 48(6)

Published: Oct. 11, 2022

Autophagy is a highly conserved process that maintains cellular homeostasis during evolution. can occur in the form of macroautophagy, microautophagy or molecular chaperone autophagy, among which macroautophagy most common. Apoptosis exists all kinds cell organisms, and kind programmed death regulated by pro‑apoptotic factors anti‑apoptotic signals. The main biological feature apoptosis activation caspase. induced variety signals, such as endoplasmic reticulum stress, induction toxic substances, stimulation pathogenic microorganisms DNA damage. Inextricable links are found between autophagy apoptosis. Studies have numerous molecules signaling pathways involved related to In addition regulating pathway also regulates interaction two achieve dynamic balance certain extent, basic physiological functions cells reduces damage body under stress. Disease occurs when disrupted. Tumors due ability avoid closely apoptosis, there must be close connection three. present review, mechanism impact their on tumorigenesis shall discussed.

Language: Английский

Citations

64
Ferroptosis and Autoimmune Diseases DOI Creative Commons
Benjamin Lai,

Chien‐Hsiang Wu,

Chao‐Yi Wu

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: June 3, 2022

Adequate control of autoimmune diseases with an unclear etiology resulting from autoreactivation the immune system remains a major challenge. One factors that trigger autoimmunity is abnormal induction cell death and inadequate clearance dead cells leads to exposure or release intracellular contents activate system. Different other subtypes, such as apoptosis, necroptosis, autophagy, pyroptosis, ferroptosis has unique association cellular iron load (but not loads metals) preserves its distinguishable morphological, biological, genetic features. This review addresses how initiated it contributes pathogenesis diseases, including systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel diseases. The mechanisms responsible for ferroptosis-associated events are discussed. We also cover perspective targeting potential therapeutic patients Collectively, this provides up-to-date knowledge regarding occurs significance in

Language: Английский

Citations

63
LncRNA-miRNA axis in tumor progression and therapy response: An emphasis on molecular interactions and therapeutic interventions DOI Open Access
Maliheh Entezari, Afshin Taheriazam,

Sima Orouei

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 154, P. 113609 - 113609

Published: Aug. 27, 2022

Epigenetic factors are critical regulators of biological and pathological mechanisms they could interact with different molecular pathways. Targeting epigenetic has been an idea approach in disease therapy, especially cancer. Accumulating evidence highlighted function long non-coding RNAs (lncRNAs) as cancer initiation development focused on their association downstream targets. microRNAs (miRNAs) the most well-known targets lncRNAs present review focuses lncRNA-miRNA axis malignancy therapy resistance tumors. LncRNA-miRNA regulates cell death such apoptosis autophagy cancers. This affects tumor metastasis via regulating EMT MMPs. Besides, determines sensitivity cells to chemotherapy, radiotherapy immunotherapy. Based studies, can be affected by drugs genetic tools this may affect expression level miRNAs targets, leading suppression/progression. LncRNAs have both tumor-promoting tumor-suppressor functions unique complicated implication therapy. also other signaling networks PI3K/Akt, STAT3, Wnt/β-catenin EZH2 among others. Notably, lncRNA/miRNA considered a signature for diagnosis prognosis

Language: Английский

Citations

54
Perineural invasion-associated biomarkers for tumor development DOI Open Access

Qi Liu,

Zhiming Ma,

Qian Cao

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 155, P. 113691 - 113691

Published: Sept. 12, 2022

Perineural invasion (PNI) is the process of neoplastic peripheral nerves and considered to be fifth mode cancer metastasis. PNI has been detected in head neck tumors pancreatic, prostate, bile duct, gastric, colorectal cancers. It leads poor prognostic outcomes high local recurrence rates. Despite increasing number studies on PNI, targeted therapeutic modalities have not proposed. The identification PNI-related biomarkers would facilitate non-invasive early diagnosis cancers, establishment panels, development approaches. In this review, we compile information molecular mediators involved PNI-associated expression significance their receptors cancers are analyzed, possible mechanisms action these explored, as well association cells microenvironment where occurs.

Language: Английский

Citations

44
Combination of DNA Damage, Autophagy, and ERK Inhibition: Novel Evodiamine-Inspired Multi-Action Pt(IV) Prodrugs with High-Efficiency and Low-Toxicity Antitumor Activity DOI
Xiaomeng Liu, Zhe Li,

Xinru Xie

et al.

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(3), P. 1852 - 1872

Published: Jan. 30, 2023

Exploring multi-targeting chemotherapeutants with advantages over single-targeting agents and drug combinations is of great significance in discovery. Herein, we employed phytogenic evodiamine (EVO) conventional Pt(II) drugs to design synthesize multi-target EVO-Pt(IV) anticancer prodrugs (4-14). Among them, compound 10 exhibited a 118-fold enhancement the IC50 value compared cisplatin low toxicity normal cells. Further studies proved that significantly enhanced intracellular Pt accumulation DNA damage, perturbed mitochondrial membrane potential, inhibited cell migration invasion, upregulated reactive oxygen species levels, induced apoptosis autophagic death. Molecular docking assay revealed fits perfectly into extracellular signal-regulated protein kinase (ERK)-1 pocket, which was verified produce profound ERK suppression. Most strikingly, superior vivo antitumor efficiency effectively attenuated systemic toxicity. Our results emphasize functionalizing platinum EVO could generate synergistically excellent activity decreased resistance, may represent brand-new cancer therapy modality.

Language: Английский

Citations

32