Talazoparib enhances the Quinacrine-mediated apoptosis in patient-derived oral mucosa CSCs by inhibiting BER pathway through the modulation of GCN5 and P300 DOI Creative Commons
Chinmay Das, Somya Ranjan Dash, Saptarshi Sinha

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 9, 2023

Abstract The presence of cancer stem cells (CSCs) in the tumor microenvironment (TME) is majorly responsible for development and recurrence cancer. Earlier reports suggested that upon DNA damage, Poly-(ADP-ribose) Polymerase-1 (PARP-1) helps chromatin modulation repair process, thereby promoting CSC survival. But whether a combination damaging agents along with PARP inhibitors can modulate assembly, inhibit processes, subsequently target CSCs not known. Hence, we have investigated effect nontoxic bioactive compound quinacrine (QC) potent inhibitor Talazoparib patient-derived oral mucosa (OM-CSCs) vivo xenograft mice preclinical model systems. Data showed QC + inhibited PARP-1-mediated remodelers’ recruitment deregulated HAT activity GCN5 (general control nonderepressible-5) P300 at damage site, preventing access proteins to damaged DNA. Additionally, this treatment topoisomerase activity, induced topological stress, apoptosis OM-CSCs. Similar results were observed an system. Collectively, data BER pathway, genomic instability triggered OM-CSCs through deregulation remodelers (GCN5 P300) activity.

Language: Английский

Self-Renewal and Pluripotency in Osteosarcoma Stem Cells’ Chemoresistance: Notch, Hedgehog, and Wnt/β-Catenin Interplay with Embryonic Markers DOI Open Access
Sara R. Martins‐Neves, Gabriela Sampaio-Ribeiro, Célia Gomes

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 8401 - 8401

Published: May 7, 2023

Osteosarcoma is a highly malignant bone tumor derived from mesenchymal cells that contains self-renewing cancer stem (CSCs), which are responsible for progression and chemotherapy resistance. Understanding the signaling pathways regulate CSC self-renewal survival crucial developing effective therapies. The Notch, Hedgehog, Wnt/β-Catenin developmental pathways, essential differentiation of normal cells, have been identified as important regulators osteosarcoma CSCs also in resistance to anticancer Targeting these their interactions with embryonic markers microenvironment may be promising therapeutic strategy overcome chemoresistance improve prognosis patients. This review focuses on role regulating self-renewal, pluripotency, chemoresistance, potential targets anti-cancer We discuss relevance markers, including SOX-2, Oct-4, NANOG, KLF4, association aforementioned overcoming drug

Language: Английский

Citations

19
Havoc in harmony: Unravelling the intricacies of angiogenesis orchestrated by the tumor microenvironment DOI
S. Acharya, Chanakya Nath Kundu

Cancer Treatment Reviews, Journal Year: 2024, Volume and Issue: 127, P. 102749 - 102749

Published: May 1, 2024

Language: Английский

Citations

7
Unravelling the Mysteries of the Sonic Hedgehog Pathway in Cancer Stem Cells: Activity, Crosstalk and Regulation DOI Creative Commons

Carlo Berrino,

Aadilah Omar

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(6), P. 5397 - 5419

Published: May 29, 2024

The Sonic Hedgehog (Shh) signalling pathway plays a critical role in normal development and tissue homeostasis, guiding cell differentiation, proliferation, survival. Aberrant activation of this pathway, however, has been implicated the pathogenesis various cancers, largely due to its regulating cancer stem cells (CSCs). CSCs are subpopulation with ability self-renew, differentiate, initiate tumour growth, contributing significantly tumorigenesis, recurrence, resistance therapy. This review focuses on intricate activity Shh within context CSCs, detailing molecular mechanisms through which influences CSC properties, including self-renewal, It further explores regulatory crosstalk between other pathways highlighting complexity network. Here, we delve into upstream regulators downstream effectors that modulate CSCs. aims cast specific focus provide detailed exploration crosstalk, discuss current developing inhibitors. By summarising key findings insights gained, wish emphasise importance elucidating interplay develop more effective therapies.

Language: Английский

Citations

4
Resveratrol nanoparticles induce apoptosis in oral cancer stem cells by disrupting the interaction between β-catenin and GLI-1 through p53-independent activation of p21 DOI
Subhasmita Bhal, Biswajit Das, Saptarshi Sinha

et al.

Medical Oncology, Journal Year: 2024, Volume and Issue: 41(7)

Published: June 4, 2024

Language: Английский

Citations

4
Identification of Molecular Markers Associated with Prostate Cancer Subtypes: An Integrative Bioinformatics Approach DOI Creative Commons
Ilaria Granata, Paola Barboro

Biomolecules, Journal Year: 2024, Volume and Issue: 14(1), P. 87 - 87

Published: Jan. 10, 2024

Prostate cancer (PCa) is characterised by androgen dependency. Unfortunately, under anti-androgen treatment pressure, castration-resistant prostate (CRPC) emerges, heterogeneous cell populations that, over time, lead to the development of different androgen-dependent or -independent phenotypes. Despite important advances in therapeutic strategies, CRPC remains incurable. Context-specific essential genes represent valuable candidates for targeted anti-cancer therapies. Through investigation gene and protein annotations integration published transcriptomic data, we identified two consensus lists stratify PCa patients’ risk discriminate phenotypes based on receptor activity. ROC Kaplan–Meier survival analyses were used set validation independent datasets. We further evaluated these their association with The deregulated expression PCa-related was associated overall disease-specific survival, metastasis and/or high recurrence risk, while CRPC-related clearly discriminated between adeno neuroendocrine Some showed context-specific essentiality. candidate drugs through a computational repositioning approach targeting treating lethal variants PCa. This work provides proof-of-concept use an integrative identify biomarkers involved progression pathogenesis within goal precision medicine.

Language: Английский

Citations

3
Talazoparib enhances the quinacrine-mediated apoptosis in patient-derived oral mucosa CSCs by inhibiting BER pathway through the modulation of GCN5 and P300 DOI
Chinmay Das, Somya Ranjan Dash, Saptarshi Sinha

et al.

Medical Oncology, Journal Year: 2023, Volume and Issue: 40(12)

Published: Nov. 8, 2023

Language: Английский

Citations

8
Effects of BYL-719 (alpelisib) on human breast cancer stem cells to overcome drug resistance in human breast cancer DOI Creative Commons

Leinan Yu,

Chuanbing Zang,

Yuanchun Ye

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 14, 2024

Introduction Breast cancer continues to be a major health concern and is currently the most commonly diagnosed worldwide. Relapse, metastasis, therapy resistance are clinical issues that doctors need address. We believe BYL-719, which PI3 kinase p110а inhibitor, could also inhibit breast stem cell phenotype epithelial-to-mesenchymal transition (EMT). In addition PI3K/AKT signaling pathway, BYL-719 can essential cancer-related pathways, all of would ultimately act on microenvironment cells, quite complicated regulates characteristics tumors. These include stemness malignant tumors, plasticity anti-apoptotic features. Materials methods A three-dimensional (3D) mammosphere culture method was used in vitro collect cells (BCSCs). MTT, clonogenic, apoptosis assays were detect viability, self-renewal, differentiation abilities. sphere formation assay under 3D conditions mammophore inhibition rate BYL-719. The subpopulation CD44 + CD24 − detected using flow cytometry analysis while EMT biomarkers pathways western blotting. All data analyzed GraphPad Prism 9 software. Results BCSC-like obtained by . confirmed proliferation cultures inhibited. PI3K/AKT/mTOR pathway inhibited Notch, JAK-STAT MAPK/ERK have crosstalk tumor (TME) By comparing eribulin-resistant lines, we effectively overcome drug resistance. Summary/conclusion novel highly effective for enriching BCSCs Furthermore, acting various pathways. Finally, targeting BCSCs. Conjugation with other anti-neoplastic agents may promising treatment this clinic.

Language: Английский

Citations

2
FTO Promotes the Stemness of Gastric Cancer Cells DOI
Mengqing Li, Xuan Wu, Li Guan

et al.

DNA and Cell Biology, Journal Year: 2023, Volume and Issue: 42(7), P. 411 - 420

Published: May 25, 2023

The full name of the FTO gene is fat mass and obesity-associated gene. In recent years, it has also been found that involved in m6A demethylation regulates progression multiple cancers, including gastric cancer. cancer stem cell theory argues cells are key factors metastasis, inhibiting expression stemness genes a good method to inhibit metastasis Currently, role regulating still unclear. By analyzing public databases, was discovered increased cancer, high associated with poor prognosis patients After were isolated, protein cells; reduced after knockdown; subcutaneous tumors nude mice smaller than those control group enhanced overexpressed by plasmid. reviewing additional literature experimental validation, we SOX2 may be factor which promotes cells. Therefore, concluded could promote cells, targeting potential therapeutic approach for metastatic CTR number: TOP-IACUC-2021-0123.

Language: Английский

Citations

4
Unravelling the role of long non-coding RNAs in modulating the Hedgehog pathway in cancer DOI

S. Chandel,

Anurag Mishra, Gaurav Dubey

et al.

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 254, P. 155156 - 155156

Published: Jan. 26, 2024

Language: Английский

Citations

1
Targeting the hedgehog pathway in MET mutation cancers and its effects on cells associated with cancer development DOI Creative Commons

Yifan Du,

Huimin Sun, Zhiyuan Shi

et al.

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Nov. 2, 2023

Abstract The mutation of MET plays a crucial role in the initiation cancer, while Hedgehog (Hh) pathway also significant cell differentiation and maintenance tumor stem cells. Conventional chemotherapy drugs are primarily designed to target majority populations within tumors rather than Consequently, after brief period remission, often relapse. Moreover, exclusive targeting stemness disregards potential for other cells regain acquire drug resistance. As result, current that solely HGF/c-MET axis Hh demonstrate only moderate efficacy specific types cancer. Mounting evidence indicates these two pathways not play important roles cancer but exert influence on development resistance single-target therapies through secretion their own ligands. In this comprehensive review, we analyze compare impact microenvironment (TME) HGF/c-MET-driven models, as well interplay between different types. Additionally, further substantiate necessity dual-pathway combination therapy critical addicted treatment.

Language: Английский

Citations

2