Emerging role of exosomes in cancer progression and tumor microenvironment remodeling

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: June 28, 2022

Abstract Cancer is one of the leading causes death worldwide, and factors responsible for its progression need to be elucidated. Exosomes are structures with an average size 100 nm that can transport proteins, lipids, nucleic acids. This review focuses on role exosomes in cancer therapy. We discuss how able modulate components tumor microenvironment influence proliferation migration rates cells. also highlight that, depending their cargo, suppress or promote cell enhance reduce response radio- chemo-therapies. In addition, we describe trigger chronic inflammation lead immune evasion by focusing ability transfer non-coding RNAs between cells other molecular signaling pathways such as PTEN PI3K/Akt cancer. Subsequently, use carriers anti-tumor agents genetic tools control progression. then tumor-derived carcinogenesis. Finally, devote a section study diagnostic prognostic clinical courses important treatment patients. provides comprehensive understanding therapy, therapeutic value remodeling microenvironment. Graphical

Language: Английский

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Targeting autophagy in prostate cancer: preclinical and clinical evidence for therapeutic response

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: March 22, 2022

Abstract Prostate cancer is a leading cause of death worldwide and new estimates revealed prostate as the in men 2021. Therefore, strategies are pertinent treatment this malignant disease. Macroautophagy/autophagy “self-degradation” mechanism capable facilitating turnover long-lived toxic macromolecules organelles. Recently, attention has been drawn towards role autophagy how its modulation provides effective therapy. In present review, we provide mechanistic discussion cancer. Autophagy can promote/inhibit proliferation survival cells. Besides, metastasis cells affected (via induction inhibition) by autophagy. affect response to therapy such chemotherapy radiotherapy, given close association between apoptosis. Increasing evidence demonstrated that upstream mediators AMPK, non-coding RNAs, KLF5, MTOR others regulate Anti-tumor compounds, for instance phytochemicals, dually inhibit or induce For improving therapy, nanotherapeutics chitosan nanoparticles have developed. With respect context-dependent cancer, genetic tools siRNA CRISPR-Cas9 be utilized targeting autophagic genes. Finally, these findings translated into preclinical clinical studies improve prognosis patients. Graphical abstract

Language: Английский

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Noncoding RNAs as regulators of STAT3 pathway in gastrointestinal cancers: Roles in cancer progression and therapeutic response

Medicinal Research Reviews, Journal Year: 2023, Volume and Issue: 43(5), P. 1263 - 1321

Published: March 23, 2023

Abstract Gastrointestinal (GI) tumors (cancers of the esophagus, gastric, liver, pancreas, colon, and rectum) contribute to a large number deaths worldwide. STAT3 is an oncogenic transcription factor that promotes genes associated with proliferation, antiapoptosis, survival, metastasis. overactivated in many human malignancies including GI which accelerates tumor progression, metastasis, drug resistance. Research recent years demonstrated noncoding RNAs (ncRNAs) play major role regulation signaling pathways pathway. The types endogenous ncRNAs are being extensively studied oncology microRNAs, long RNAs, circular RNAs. These can either be tumor‐promoters or tumor‐suppressors each one them imparts their activity via different mechanisms. pathway also tightly modulated by ncRNAs. In this article, we have elaborated on tumor‐promoting tumors. Subsequently, comprehensively discussed as well suppressor functions mechanism action known modulate cancers.

Language: Английский

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Circulating tumor cells: from new biological insights to clinical practice

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 2, 2024

Abstract The primary reason for high mortality rates among cancer patients is metastasis, where tumor cells migrate through the bloodstream from original site to other parts of body. Recent advancements in technology have significantly enhanced our comprehension mechanisms behind bloodborne spread circulating (CTCs). One critical process, DNA methylation, regulates gene expression and chromosome stability, thus maintaining dynamic equilibrium Global hypomethylation locus-specific hypermethylation are examples changes methylation patterns that pivotal carcinogenesis. This comprehensive review first provides an overview various processes contribute formation CTCs, including epithelial-mesenchymal transition (EMT), immune surveillance, colonization. We then conduct in-depth analysis how modifications within CTCs impact each these stages during CTC dissemination. Furthermore, we explored potential clinical implications with cancer. By understanding epigenetic modifications, can gain insights into metastatic process identify new biomarkers early detection, prognosis, targeted therapies. aims bridge gap between basic research application, highlighting significance context metastasis offering avenues improving patient outcomes.

Language: Английский

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Cannabidiol activates MAPK pathway to induce apoptosis, paraptosis, and autophagy in colorectal cancer cells

Journal of Cellular Biochemistry, Journal Year: 2024, Volume and Issue: 125(4)

Published: Feb. 15, 2024

Abstract Mitogen‐activated protein kinase (MAPK) activation by natural compounds is known to be involved in the induction of apoptosis, paraptosis, and autophagy. Cannabidiol (CBD), a bioactive compound found Cannabis sativa , endowed with many pharmacological activities. We investigated cytotoxic effect CBD panel colorectal cancer (CRC) cells (HT‐29, SW480, HCT‐116, HCT‐15). induced significant cytotoxicity as evidenced results MTT assay, live‐dead flow cytometric analysis. Since displayed against CRC cells, we examined on decreased expression antiapoptotic proteins increased Annexin‐V‐positive well TUNEL‐positive suggesting that induces apoptosis. ATF4 (activating transcription factor 4) CHOP (CCAAT/enhancer‐binding homologous protein), elevated endoplasmic reticulum stress, enhanced reactive oxygen species levels indicating also promotes paraptosis. Atg7, phospho‐Beclin‐1, LC3 accelerates Since, MAPK pathway common cascade regulation autophagy, JNK, p38, ERK pathways. activated all forms inhibition these reverted observed effects. Our findings implied could induce cell death activating autophagy through pathway.

Language: Английский

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Fangchinoline inhibits non-small cell lung cancer metastasis by reversing epithelial-mesenchymal transition and suppressing the cytosolic ROS-related Akt-mTOR signaling pathway

Cancer Letters, Journal Year: 2022, Volume and Issue: 543, P. 215783 - 215783

Published: June 11, 2022

Language: Английский

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Deciphering JAK/STAT signaling pathway: A multifaceted approach to tumorigenesis, progression and therapeutic interventions

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 131, P. 111846 - 111846

Published: March 23, 2024

Language: Английский

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Fangchinoline eliminates intracellular Salmonella by enhancing lysosomal function via the AMPK-mTORC1-TFEB axis

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Salmonella, a foodborne zoonotic pathogen, is significant cause of morbidity and mortality in animals humans globally. With the prevalence multidrug-resistant strains, Salmonellosis has become formidable challenge. Host-directed therapy (HDT) recently emerged as promising anti-infective approach for treating intracellular bacterial infections. Plant-derived natural products, owing to their structural functional diversity, are increasingly being explored utilized encouraging candidates HDT compounds. This study aims identify screen compounds with potential treatment Salmonella A cell-based screening was deployed capable mitigating replication S. enterica. Safety efficacy candidate were evaluated using multiple animal models. RNA sequencing, ELISA, immunoblotting analyses conducted elucidate underlying mechanisms action. Our results reveal that fangchinoline (FAN) effectively reduces enterica survival both vitro vivo. Meanwhile, FAN also displays activity against other pathogens, including isolates. 14-day safety evaluation mice showed no toxic or adverse effects from administration. sequencing analysis reveals an upregulation lysosome pathways enterica-infected cells treated FAN. Mechanistic studies indicate increases acid lysosomal quantities fosters autophagic response Salmonella-infected AMPK-mTORC1-TFEB axis. In addition, alleviates inflammatory by inactivating NF-κB pathway. findings suggest represents lead compound tackling recalcitrant infections caused pathogens.

Language: Английский

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Deciphering STAT3 signaling potential in hepatocellular carcinoma: tumorigenesis, treatment resistance, and pharmacological significance

Cellular & Molecular Biology Letters, Journal Year: 2023, Volume and Issue: 28(1)

Published: April 21, 2023

Abstract Hepatocellular carcinoma (HCC) is considered one of the greatest challenges to human life and most common form liver cancer. Treatment HCC depends on chemotherapy, radiotherapy, surgery, immunotherapy, all which have their own drawbacks, patients may develop resistance these therapies due aggressive behavior cells. New effective for can be developed by targeting molecular signaling pathways. The expression signal transducer activator transcription 3 (STAT3) in cancer cells changes, during progression, tends increase. After induction STAT3 growth factors cytokines, phosphorylated translocated nucleus regulate progression. concept current review revolves around phosphorylation status HCC, studies show that high progression HCC. This addresses function as an oncogenic factor able prevent apoptosis thus promote Moreover, regulates both survival- death-inducing autophagy promotes metastasis inducing epithelial–mesenchymal transition (EMT). In addition, upregulation associated with occurrence chemoresistance radioresistance Specifically, non-protein-coding transcripts inhibition antitumor agents affect tumor this review, topics are discussed detail provide further insight into role tumorigenesis, treatment resistance, pharmacological regulation Graphical

Language: Английский

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Kaempferide triggers apoptosis and paraptosis in pancreatic tumor cells by modulating the ROS production, SHP‐1 expression, and the STAT3 pathway

IUBMB Life, Journal Year: 2024, Volume and Issue: 76(9), P. 745 - 759

Published: May 6, 2024

Abstract Pancreatic cancer is one of the deadliest diseases with a poor prognosis and five‐survival rate. The STAT3 pathway hyperactivated which contributes to sustained proliferative signals in pancreatic cells. We have isolated kaempferide (KF), an O ‐methylated flavonol, from green propolis Mimosa tenuiflora examined its effect on two forms cell death namely, apoptosis paraptosis. KF significantly increased cleavage caspase‐3 PARP. It also downmodulated expression Alix (an intracellular inhibitor paraptosis) CHOP ATF4 (transcription factors that promote indicating promotes as well reactive oxygen species (ROS) suggesting perturbance redox state. N‐acetylcysteine reverted apoptosis‐ paraptosis‐inducing effects KF. Some ROS inducers are known suppress investigation revealed downmodulates upstream kinases (JAK1, JAK2, Src). Additionally, elevated SHP‐1, tyrosine phosphatase involved negative modulation pathway. Knockdown SHP‐1 prevented KF‐driven inhibition. Altogether, has been identified promoter paraptosis cells through elevation generation expression.

Language: Английский

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