Understanding MAPK Signaling Pathways in Apoptosis

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(7), P. 2346 - 2346

Published: March 28, 2020

MAPK (mitogen-activated protein kinase) signaling pathways regulate a variety of biological processes through multiple cellular mechanisms. In most these processes, such as apoptosis, MAPKs have dual role since they can act activators or inhibitors, depending on the cell type and stimulus. this review, we present main pro- anti-apoptotic mechanisms regulated by MAPKs, well crosstalk observed between some MAPKs. We also describe basic properties (ultrasensitivity, hysteresis, digital response), presence different positive feedback loops in apoptosis. provide simple guide to predict MAPKs’ behavior, based intensity duration Finally, consider osmostress-induced apoptosis using Xenopus oocytes model. As will see, is plagued with loops. hope review help understand how engage irreversible decisions.

Language: Английский

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Targeting MAPK Signaling in Cancer: Mechanisms of Drug Resistance and Sensitivity

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(3), P. 1102 - 1102

Published: Feb. 7, 2020

Mitogen-activated protein kinase (MAPK) pathways represent ubiquitous signal transduction that regulate all aspects of life and are frequently altered in disease. Here, we focus on the role MAPK modulating drug sensitivity resistance cancer. We briefly discuss new findings extracellular signaling-regulated (ERK) pathway, but mainly mechanisms how stress activated pathways, such as p38 Jun N-terminal kinases (JNK), impact response cancer cells to chemotherapies targeted therapies. In this context, also metabolic epigenetic aberrations therapeutic opportunities arising from these changes.

Language: Английский

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Heavy metal associated health hazards: An interplay of oxidative stress and signal transduction

Chemosphere, Journal Year: 2020, Volume and Issue: 262, P. 128350 - 128350

Published: Sept. 16, 2020

Language: Английский

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JNK signaling in cancer cell survival

Medicinal Research Reviews, Journal Year: 2019, Volume and Issue: 39(6), P. 2082 - 2104

Published: March 25, 2019

c-Jun N-terminal kinase (JNK) is involved in cancer cell apoptosis; however, emerging evidence indicates that this Janus signaling promotes survival. JNK acts synergistically with NF-κB, JAK/STAT, and other molecules to exert a survival function. positively regulates autophagy counteract apoptosis, its effect on related the development of chemotherapeutic resistance. The prosurvival may involve an immune evasion mechanism mediated by transforming growth factor-β, toll-like receptors, interferon-γ, autophagy, as well compensatory JNK-dependent proliferation. present review focuses recent advances understanding function role tumor chemoresistance, including comprehensive analysis molecular mechanisms underlying JNK-mediated There focus specific "Yin Yang" functions JNK1 JNK2 regulation We highlight our knowledge roles survival, which provide insight into distinct potential for therapy.

Language: Английский

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Metformin induces cell cycle arrest, apoptosis and autophagy through ROS/JNK signaling pathway in human osteosarcoma

International Journal of Biological Sciences, Journal Year: 2019, Volume and Issue: 16(1), P. 74 - 84

Published: Dec. 6, 2019

Metformin, an ancient drug commonly used for treating type II diabetes, has been associated to anti-cancer capacity in a variety of developing cancers, though the mechanism remains elusive. Here, we aimed examine inhibitory effect metformin osteosarcoma. Herein, demonstrated that treatment blocked proliferation progression by causing accumulation G2/M phase U2OS and 143B cells. Furthermore, triggered programmed cell death process osteosarcoma lines. Further research indicated induction apoptosis autophagy could remarkably attenuate after ROS scavenger NAC JNK inhibitor SP600125. Additionally, our results showed NAC-suppressed JNK/c-Jun signaling pathway have activated through treatment. Lastly, inhibit growth under safe dose vivo. Thus, propose induce cycle arrest as well death, including autophagy, ROS-dependent cascade human This metformin-induced provides further insights into its antitumor potential molecular illuminates cancer targets

Language: Английский

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Selective inhibitors for JNK signalling: a potential targeted therapy in cancer

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2020, Volume and Issue: 35(1), P. 574 - 583

Published: Jan. 1, 2020

c-Jun N-terminal kinase (JNK) signalling regulates both cancer cell apoptosis and survival. Emerging evidence show that JNK promoted tumour progression is involved in various cancers, include human pancreatic-, lung-, breast cancer. The pro-survival oncoprotein functions a context- type-specific manner to affect signal pathways modulate initiation, proliferation, migration. therefore considered potential oncogenic target for therapy. Currently, designing effective specific inhibitors an active area the treatment. Some ATP-competitive of JNK, such as SP600125 AS601245, are widely used vitro; however, this type inhibitor lacks specificity they indiscriminately inhibit phosphorylation all substrates. Moreover, has at least three isoforms with different development identifying selective crucial targeted therapy identified; their clinical studies relatively less conducted. In review, we first summarised function progression; there focus on discussion novel targeting Finally, have offered future perspective context therapies. We hope review will help further understand role provide insight into design

Language: Английский

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Type I AIE photosensitizers: Mechanism and application

View, Journal Year: 2021, Volume and Issue: 3(2)

Published: July 13, 2021

Abstract Photodynamic therapy (PDT) with plenty of advantages is expected to become a promising modality for cancer treatment, but challenges still remain. In the past decade, abundant photosensitizers (PSs) aggregation‐induced emission (AIE) property make development PSs enter upon new phase, offering incomparable merits. Recently, Type I AIE capability generating radical reactive oxygen species (ROS) have emerged as strong candidates overcome inherent hypoxia nature solid tumors. this review, detailed discussions on mechanisms PDT are drawn highlight basic pathway over II one in hypoxic PDT, followed by summary frequently‐used detection methods accurate distinguishing ROS. Finally, latest representative advances summarized, and future perspectives discussed.

Language: Английский

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Impact of Complex Apoptotic Signaling Pathways on Cancer Cell Sensitivity to Therapy

Cancers, Journal Year: 2024, Volume and Issue: 16(5), P. 984 - 984

Published: Feb. 28, 2024

Anticancer drugs induce apoptotic and non-apoptotic cell death in various cancer types. The signaling pathways for anticancer drug-induced have been shown to differ between drug-sensitive drug-resistant cells. In atypical multidrug-resistant leukemia cells, the c-Jun/activator protein 1 (AP-1)/p53 pathway leading is altered. Cancer cells treated with undergo c-Jun/AP-1–mediated are involved c-Jun N-terminal kinase activation growth arrest- DNA damage-inducible gene 153 (Gadd153)/CCAAT/enhancer-binding homologous induction, regardless of p53 genotype. Gadd153 induction associated mitochondrial membrane permeabilization after drug treatment involves a coupled endoplasmic reticulum stress response. apoptosis by mediated intrinsic (cytochrome c, Cyt c) subsequent caspase cascade via proapoptotic genes (e.g., Bax Bcl-xS) their interactions. caspase-dependent caspase-independent occurs extrinsic pathways. targeting antiapoptotic such as Bcl-2 enhances efficacy. modulation Bcl-xS transduction increases sensitivity multidrug resistance-related protein-overexpressing epidermoid carcinoma drugs. significance autophagy therapy remains be elucidated. this review, we summarize current knowledge death-related alterations during discuss potential strategies enhance

Language: Английский

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Cell-death induced immune response and coagulopathy promote cachexia in Drosophila

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Tumors can exert a far-reaching influence on the body, triggering systemic responses that contribute to debilitating conditions like cancer cachexia. To characterize mechanisms underlying tumor-host interactions, we utilized BioID-based proximity labeling method identify proteins secreted by Yki act adult Drosophila gut tumors into bloodstream/hemolymph. Among major identified are coagulation and immune-responsive factors wasting phenotypes associated with tumors. The effect of innate immunity is mediated NFκB transcription Relish, dorsal, Dif, which in turn upregulate expression cachectic Pvf1, Impl2, Upd3. In addition, secrete Eiger, TNF-alpha homolog, activates JNK signaling pathway neighboring non-tumor cells, leading cell death. release damage-associated molecular patterns (DAMPs) from these dying cells presumably amplifies inflammatory response, exacerbating wasting. Targeting pathway, or production could potentially alleviate effects

Language: Английский

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eIF2α-CHOP-BCl-2/JNK and IRE1α-XBP1/JNK signaling promote apoptosis and inflammation and support the proliferation of Newcastle disease virus

Cell Death and Disease, Journal Year: 2019, Volume and Issue: 10(12)

Published: Nov. 26, 2019

Abstract Newcastle disease virus (NDV) causes severe infectious in poultry and selectively kills tumor cells, by inducing apoptosis cytokines secretion. In this report, we study the mechanisms underlying NDV-induced investigating unfolded protein response (UPR). We found that NDV infection activated all three branches of UPR signaling (PERK-eIF2α, ATF6, IRE1α) triggered apoptosis, avian cells (DF-1 CEF) various human cancer cell types (HeLa, Cal27, HN13, A549, H1299, Huh7, HepG2). Interestingly, suppression either or led to impaired proliferation. Meanwhile, inhibition 4-PBA protected from apoptosis. Further revealed activation PERK-eIF2α induced expression transcription factor CHOP, which subsequently promoted downregulating BCL-2/MCL-1, promoting JNK suppressing AKT signaling. parallel, IRE1α mediated splicing XBP1 mRNA resulted translation nuclear translocation XBP1s, thereby ER chaperones components ER-associated degradation (ERAD). Furthermore, secretion via Knock down overexpression studies showed IRE1α, XBP1, supported efficient Our demonstrates induction eIF2α-CHOP-BCL-2/JNK IRE1α-XBP1/JNK cascades promote secretion, these support

Language: Английский

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