Unveiling the impact of CD133 on cell cycle regulation in radio- and chemo-resistance of cancer stem cells

Frontiers in Public Health, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 6, 2025

The adaptation of malignancy to therapy presents a significant challenge in cancer treatment. cell cycle plays crucial role regulating the evolution radio- and chemo-resistance tumor cells. Cancer stem cells (CSCs) are primary source resistance, with CD133 being one most recognized valuable surface markers CSCs. Evidence increasingly suggests that is associated resistance. current understanding molecular biological function limited, leading ongoing debates about its biology. In this review, we explore recent research emerging trends related through extensive literature content analysis. It was summarized new insights into relationships signaling pathways resistant aim review provide foundational how these their interactions impact prognosis inform treatment strategies.

Language: Английский

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Cyclophilin A: promising target in cancer therapy

Cancer Biology & Therapy, Journal Year: 2024, Volume and Issue: 25(1)

Published: Nov. 8, 2024

Cyclophilin A (CypA), a member of the immunophilin family, stands out as most prevalent among cyclophilins found in humans. Beyond serving intracellular receptor for immunosuppressive drug cyclosporine (CsA), CypA exerts critical functions within cell via its

Language: Английский

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PPIA enhances cell growth and metastasis through CD147 in oral cancer

Archives of Biochemistry and Biophysics, Journal Year: 2025, Volume and Issue: 765, P. 110328 - 110328

Published: Feb. 6, 2025

Language: Английский

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Discovery of Novel Oxazolo[4,3-f]purine Derivatives as Antitumor Agents through PPIA Interaction

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

54 novel oxazolo [4,3-f]purine derivatives were designed, synthesized, and evaluated for antitumor activity, among which compound 20b exhibited potent activity against several cancer cell lines. Compound inhibited metastasis, arrested the cycle in G0/G1 phase, induced apoptosis HCT116 cells. Mechanistic studies revealed that increased ROS levels led to DNA damage, endoplasmic reticulum (ER) stress, mitochondrial dysfunction Limited proteolysis-small molecule mapping (LiP-SMap), drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), surface plasmon resonance (SPR) experiments provided evidence bound PPIA with a KD value of 0.52 μM. siRNA indicated 20b-mediated antiproliferative antimigration activities abolished PPIA/MAPK signaling pathway was when silenced Significantly, presented significant anticolorectal efficacy vivo without obvious toxicity. These results indicate may serve as anticancer agent targeting PPIA, meriting further attention research.

Language: Английский

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Hotspots and trends in gastric cancer stem cell research: a visualization and bibliometric analysis

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: March 5, 2025

Gastric cancer (GC) is a type of malignant tumor that seriously endangers human health. As the understanding mechanisms underlying gastric deepens, in recent years, investigations on stem cells (GCSCs) have garnered significant interest. They are pivotal onset, progression, recurrence, and pharmacoresistance GC. Comprehensive research GCSCs expected to provide new strategies for diagnosis treatment This article endeavors comprehensively assess current status future trends through bibliometric analysis, thereby providing valuable reference further - depth studies this field. English language academic journals related Web Science database were retrieved. Subsequently, VOSviewer was utilized conduct network collinear analysis exported source institutions, literature authors, references, keywords. And CiteSpace used perform statistical annual publication count, keyword clustering, burst. A total 3882 documents met criteria incorporated. The quantity published papers has shown consistent upward trend annually since 2003. Among authors literature, multiple stable core author groups represented by Zhu, Wei, Wang, Mei, Xu, Wenrong, etc. been formed. There 335 associated institutions total. Japan National Cancer Center strongest relevance largest number papers. 7 clustering labels formed among keywords, including main modules such as activation, cells, DNA content aneuploidy, expression. 25 burst keywords generated, past two years include mesenchymal drug resistance, proliferation, emergence references indicates eight cited up now focus research. overview 30 visually presented visual maps. In decade, scholars' field gradually intensified, development good. Through deeper study mechanism, intervention will be promising approach GC patients. hot topic still deserves more attention future.

Language: Английский

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Mycoplasma genitalium protein of adhesion inhibits human urethral epithelial cells apoptosis via CypA/PI3K/AKT/mTOR-dependent autophagy

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: March 26, 2025

Background Mycoplasma genitalium , a prokaryotic microorganism, is known pathogen of sexually transmitted infections. Previously, we identified cyclophilin A (CypA) as the membrane receptor on human urethral epithelial cells (SV-HUC-1) that binds to M. protein adhesion (MgPa) and demonstrated recombinant MgPa (rMgPa) inhibits apoptosis via CypA-mediated regulation PI3K/AKT/NF-κB pathway. Given established interplay between autophagy apoptosis, this study aims investigate whether rMgPa in SV-HUC-1 by modulating CypA/PI3K/AKT/mTOR-dependent autophagy. Methods In work, after were stimulated with rMgPa, was detected using Western blotting, immunofluorescence transmission electron microscopy, respectively. blotting Annexin V/PI assays used determine signaling pathway involved rMgPa- inhibited inducing Results upregulated autophagy-related proteins ATG7 LC3B while downregulating P62 expression cells. Transmission microscopy showed presence intracellular autophagosomes, indirect confirmed enhanced LC3B, indicating induces Silencing CypA significantly attenuated rMgPa-induced autophagy, highlighting essential role process. Furthermore, found regulate PI3K/AKT/mTOR CypA, thereby promoting blot analysis urothelial through CypA-dependent mechanism. Conclusion This demonstrates suppresses modulation pathway, which elucidates novel survival strategy employed within host provides valuable insights for potential therapeutic interventions targeting

Language: Английский

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Molecular targets and mechanisms of traditional Chinese medicine combined with chemotherapy for gastric cancer: a meta-analysis and multi-omics approach

Annals of Medicine, Journal Year: 2025, Volume and Issue: 57(1)

Published: May 3, 2025

The combination of traditional Chinese medicine (TCM) with chemotherapy has been widely applied in the treatment gastric cancer (GC). However, previous clinical studies have constrained by small sample sizes and a lack investigation into molecular mechanisms TCM. This study aims to assess efficacy TCM treating GC leveraging strengths meta-analysis multi-omics approaches while also summarizing underlying pharmacological mechanisms. A systematic literature review were conducted using online databases collect data before May 2024. was investigate association between combined prognosis GC. targets high-frequency TCMs identified through network pharmacology. investigated multi-omics. 9 2,158 patients included. results demonstrated that significantly improved overall survival (OS) (OR = 2.91; 95% CI: 2.70-3.12, p < 0.00001) enhanced their quality life 4.00; 1.99-8.03, 0.0001). Network pharmacology analysis 13 potential GC; additionally, highlighted significant roles MK, MIF, GALECTIN, CypA signaling pathways improves future research can focus on these key pathways. supports application precision suggests rational use managing

Language: Английский

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Bufotalin Suppresses Proliferation and Metastasis of Triple-Negative Breast Cancer Cells by Promoting Apoptosis and Inhibiting the STAT3/EMT Axis

Molecules, Journal Year: 2023, Volume and Issue: 28(19), P. 6783 - 6783

Published: Sept. 23, 2023

Triple-negative breast cancer (TNBC) is a highly aggressive type of and has poor prognosis. As standardized TNBC treatment regimens cause drug resistance tumor recurrence, the development new strategies urgently required. Bufotalin bufadienolide isolated from skin parotid venom glands toad Bufo gargarizan, several pharmacological properties, including antiviral, anti-inflammatory, anticancer activities. However, effect underlying molecular mechanisms action bufotalin in have not been fully studied. In current study, we investigated effects on growth metastasis MDA-MB-231 HCC1937 cells. potently inhibited proliferation both cell lines by promoting cycle arrest caspase-mediated apoptosis. Furthermore, effectively suppressed migration invasion regulating expression key epithelial-mesenchymal transition (EMT) biomarkers, matrix metalloproteinases (MMPs), integrin α6. Notably, cells was associated with downregulation signal transducer activator transcription 3 (STAT3) signaling pathway. Collectively, our results suggest that natural compound may exert antiproliferative antimetastatic activities modulating apoptotic pathway STAT3/EMT axis.

Language: Английский

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Inhibition of PRMT1 Suppresses the Growth of U87MG-Derived Glioblastoma Stem Cells by Blocking the STAT3 Signaling Pathway

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2950 - 2950

Published: March 3, 2024

Glioblastoma stem cells (GSCs) play a pivotal role in the initiation, progression, resistance to treatment, and relapse of glioblastoma multiforme (GBM). Thus, identifying potential therapeutic targets drugs that interfere with growth GSCs may contribute improved treatment outcomes for GBM. In this study, we first demonstrated functional protein arginine methyltransferase 1 (PRMT1) GSC growth. Furamidine, PRMT1 inhibitor, effectively inhibited proliferation tumorsphere formation U87MG-derived by inducing cell cycle arrest at G0/G1 phase promoting intrinsic apoptotic pathway. Moreover, furamidine potently suppressed vivo tumor U87MG chick embryo chorioallantoic membrane model. particular, inhibitory effect on was associated downregulation signal transducer activator transcription 3 (STAT3) key markers, including CD133, Sox2, Oct4, Nanog, aldehyde dehydrogenase 1, integrin α6. Our results also showed knockdown small interfering RNA significantly vitro through molecular mechanism similar furamidine. addition, combined berbamine, calcium/calmodulin-dependent kinase II gamma (CaMKIIγ) more strongly than single-compound treatment. The increased antiproliferative combining two compounds resulted from stronger STAT3-mediated downstream GBM stemness regulators dual CaMKIIγ function blockade. conclusion, these findings suggest its furamidine, are novel drug candidates suppressing

Language: Английский

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Inhibitors of Cyclophilin A: Current and Anticipated Pharmaceutical Agents for Inflammatory Diseases and Cancers

Molecules, Journal Year: 2024, Volume and Issue: 29(6), P. 1235 - 1235

Published: March 11, 2024

Cyclophilin A, a widely prevalent cellular protein, exhibits peptidyl-prolyl cis-trans isomerase activity. This protein is predominantly located in the cytosol; additionally, it can be secreted by cells response to inflammatory stimuli. A has been identified key player many of biological events and therefore involved several diseases, including vascular immune disorders, aging, cancers. It represents an attractive target for therapeutic intervention with small molecule inhibitors such as cyclosporin A. Recently, number novel cyclophilin have emerged. However, remains elusive whether how function diseases In this review, we discuss current available data about inhibitors, its derivatives, quinoxaline peptide analogues, outline most recent advances clinical trials these agents. Inhibitors are poised enhance our comprehension molecular mechanisms that underpin cancers associated advancement will aid development innovative pharmaceutical treatments future.

Language: Английский

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