In silico Assessment of Phytochemicals from Selected Plants as Prospective TGF‐β1 Inhibitors for Prostate Cancer Therapy DOI

Felix Oluwasegun Ishabiyi,

Rukayat Yetunde Omotosho‐Sanni,

Soukayna Baammi

et al.

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(40)

Published: Oct. 23, 2024

Abstract Transforming growth factor β1 (TGF‐β) is a cytokine with pleiotropic biological functions. Recently, its signaling pathway has been highlighted for implicative paradoxical roles in prostate cancer (PCa). Suppressing downstream effects of this by interfering receptor complex formation through inhibition the TGF‐β1 leads to antitumor effects, illuminating as viable therapeutic target PCa. Our compound library—established literature‐based approach that identified phytochemicals published evidence against TGF‐β1—was screened employing molecular docking, density functional theory (DFT), and dynamic (MD) simulations identify inhibitors. Eight 24 docked from our library had good binding affinity (ranging −11.7 −10 kcal/mol) (PDB: 1PY5). The displayed stability reactivity revealed DFT analysis desirable pharmacokinetic profile. top four phytochemical complexes high energies maintained throughout 100 ns simulation. Qualitative studies on drug repurposing attributes bisindolylmaleimide, flavopiridol, baicalin, gefitinib inhibitors are recommended; most importantly, suggest further wet‐lab corroborate these phytochemicals—SB 202190, SB 203580, silymarin, cryptotanshinone—in targeted development.

Language: Английский

The role of innate immune cells in modulating vascular dynamics in skin malignancies DOI Creative Commons

Mateusz Marciniak,

Martyna Stachowicz-Suhs, Marek Wagner

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 189331 - 189331

Published: April 1, 2025

A developing tumor relies heavily on blood vessels to supply oxygen and nutrients. As a result, angiogenesis, the formation of new vessels, supports growth progression. Similarly, lymphangiogenesis, lymphatic plays critical role in metastatic dissemination by providing pathways for malignant cells spread. The microenvironment is crucial establishing maintaining these vascular networks, with innate immune playing key regulatory role. Notably, are specifically enriched barrier tissues, such as skin, emphasizing their importance skin malignancies Therefore, understanding regulating angiogenesis lymphangiogenesis essential novel therapeutic strategies. This review article explores how influence vasculature highlights potential that may arise from this knowledge.

Language: Английский

Citations

0
Immune mediated support of metastasis: Implication for bone invasion DOI Creative Commons
Zengfeng Xin,

Luying Qin,

Yang Tang

et al.

Cancer Communications, Journal Year: 2024, Volume and Issue: 44(9), P. 967 - 991

Published: July 14, 2024

Abstract Bone is a common organ affected by metastasis in various advanced cancers, including lung, breast, prostate, colorectal, and melanoma. Once patient diagnosed with bone metastasis, the patient's quality of life overall survival are significantly reduced owing to wide range morbidities increasing difficulty treatment. Many studies have shown that closely related microenvironment, especially immune microenvironment. However, effects cells microenvironment on remain unclear. Here, we described changes during discussed their mechanisms. Osteoblasts, adipocytes, other non‐immune were also included. This review summarized existing treatment methods potential therapeutic targets, provided insights for future cancer metastasis.

Language: Английский

Citations

3
Targeting Lipid Metabolism in Cancer Stem Cells for Anticancer Treatment DOI Open Access
Manish Kumar Singh,

Sunhee Han,

Sung Soo Kim

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(20), P. 11185 - 11185

Published: Oct. 17, 2024

Cancer stem cells (CSCs), or tumor-initiating (TICs), are small subpopulations (0.0001-0.1%) of cancer that crucial for relapse and therapy resistance. The elimination each CSC is essential achieving long-term remission. Metabolic reprogramming, particularly lipids, has a significant impact on drug efficacy by influencing diffusion, altering membrane permeability, modifying mitochondrial function, adjusting the lipid composition within CSCs. These changes contribute to development chemoresistance in various cancers. intricate relationship between metabolism resistance CSCs an emerging area research, as different species play roles multiple stages autophagy. However, link autophagy context regulation remains unclear. Understanding interplay reprogramming could lead new approaches enhancing therapies reducing tumorigenicity these cells. In this review, we explore latest findings CSCs, including role key regulatory enzymes, inhibitors, contribution maintaining homeostasis. recent may provide critical insights identifying novel pharmacological targets effective anticancer treatment.

Language: Английский

Citations

3
NK Cell‐Based Cancer Immunotherapies: Current Progress, Challenges and Emerging Opportunities DOI
Mohammad Y. Alshahrani, Subasini Uthirapathy, Abhinav Kumar

et al.

Journal of Biochemical and Molecular Toxicology, Journal Year: 2024, Volume and Issue: 38(11)

Published: Nov. 1, 2024

Natural killer (NK) cells are vital innate immune that play a crucial role in cancer therapy. They targeted by therapies designed to modulate, retain, and enhance their antitumor function vivo. In addition whole-cell therapy, NK cell-derived exosomes (NDEs) offer high safety easily subject chemical, biological, immunological modifications. This makes them suitable for use combination with various current efficacy, treatment outcomes, reduce side effects review aims outline summarizes the potential of cells, as well challenges opportunities cell-based immunotherapies such allogeneic autologous cell transplantation, CAR cytokines monoclonal antibodies. The also explores dual regulatory tumor on highlights NDEs, either alone or other therapies, reprogram immunosuppressive microenvironment expedite therapeutic immunotherapy future clinical research.

Language: Английский

Citations

2
Exploring the potential of TGFβ as a diagnostic marker and therapeutic target against cancer DOI Creative Commons
Pankaj Kumar Garg, Siddhika Pareek, Prakash Kulkarni

et al.

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 231, P. 116646 - 116646

Published: Nov. 20, 2024

Language: Английский

Citations

2
Design, Synthesis, and Activity of a Novel Series of Pyridazine-Based ALK5 Inhibitors DOI
Daniele Pala,

Paolo Ronchi,

Donatella Rescigno

et al.

ACS Medicinal Chemistry Letters, Journal Year: 2024, Volume and Issue: 15(11), P. 1925 - 1932

Published: Oct. 23, 2024

ALK5 inhibitors represent an attractive therapeutic approach for the treatment of a variety pathologies, including cancer and fibrosis. Herein, we report design

Language: Английский

Citations

1
New therapeutic approaches for fibrosis: harnessing translational regulation DOI
S.S. Gill, Richard H. Gomer

Trends in Molecular Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

Citations

1
Tumor-derived colorectal cancer organoids induce a unique Treg cell population through direct modulation of CD4+ T cell differentiation. DOI

Sonia Aristín Revilla,

Cynthia Lisanne Frederiks,

Stefan Prekovic

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 22, 2024

Abstract In colorectal cancer (CRC), increased numbers of tumor-infiltrating CD4 + regulatory T (Treg) cells correlate with tumor development and immunotherapy failure, leading to poor prognosis. However, the molecular cellular mechanisms governing Treg recruitment, expansion, or differentiation remain unclear. Here, we developed an in vitro co-culture system assess capacity CRC tumors directly modulate cell differentiation. from Foxp3eGFP mice were co-cultured murine tumor-derived organoids, resulting a significant increase numbers. This induction was not due proliferation, but rather through TGFβ-dependent manner. Human organoids similarly induced that exhibited enhanced suppressive compared TGFβ-induced cells. RNA-sequencing analysis identified distinct transcriptional profiles between organoid-induced cells, upregulation key functional signature genes linked vivo . High expression upregulated correlates shorter progression free interval overall survival patients, highlighting their prognostic potential. Taken together, drive phenotype resembling model can be applied both understand by which identify approaches disrupt function stimulate anti-tumor immunity.

Language: Английский

Citations

0
The anti-inflammatory and tolerogenic potential of small spleen peptides DOI Creative Commons
Viktor Wixler,

Igor Z. Zaytsev,

Yvonne Boergeling

et al.

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

Published: Sept. 2, 2024

Maintaining peripheral immune tolerance and preventing harmful autoimmune reactions is a fundamental task of the system. However, these essential functions are significantly compromised during disorders, creating major challenge in treating conditions. In this context, we provide an overview research on small spleen polypeptides (SSPs) that naturally regulate tolerance. Alongside outlining observed effects SSPs, summarize here findings cellular molecular mechanisms underlie their regulatory impact. Specifically, SSPs have demonstrated remarkable effectiveness halting progression developing or established disorders like psoriasis arthritis animal models. They primarily target dendritic cells (DCs), swiftly prompting production extracellular ATP, which then degraded sensed by adenosine receptors. This process triggers mTOR signaling cascade, similar to powerful triggers, but instead rapid intense reaction, it leads moderate yet significant activation cascade. induces tolerogenic state cells, ultimately leading generation Foxp3 + immunosuppressor Treg cells. addition, may indirectly attenuate response reducing ATP synthesis non-immune such as endothelial when exposed elevated levels proinflammatory cytokines. thus potential contribute restoration offer valuable therapeutic benefits diseases.

Language: Английский

Citations

0
Emerging druggable targets for immune checkpoint modulation in cancer immunotherapy: the iceberg lies beneath the surface DOI
Sakuntala Gayen, Swarupananda Mukherjee, Sandipan Dasgupta

et al.

APOPTOSIS, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

0