Anti-Angiogenic Potential of Marine Streptomyces-Derived Lucknolide A on VEGF/VEGFR2 Signaling in Human Endothelial Cells DOI Creative Commons
Byeoung-Kyu Choi,

Min-Hee Jo,

Hee Jae Shin

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(5), P. 987 - 987

Published: Feb. 20, 2025

Angiogenesis, primarily driven by the vascular endothelial growth factor (VEGF) and its receptor, VEGFR, plays a key role in various pathological processes such as cancer progression. Here, we investigated anti-angiogenic effects of Lucknolide A (LA), marine Streptomyces-derived compound, evaluated potential VEGFR2 inhibitor. LA selectively inhibited proliferation human cells EA.hy926 HUVEC while exhibiting minimal on normal fibroblasts tumor cells. induced S-phase cell cycle arrest apoptosis cells, increasing apoptotic markers p53, Bax, p21 decreasing anti-apoptotic protein Bcl-2, with these being further enhanced under VEGF stimulation. Additionally, suppressed phosphorylation downstream signaling pathways, including Akt/mTOR/p70S6K, MEK/ERK, Src, FAK, p38 MAPK, which are crucial for survival angiogenesis. Molecular docking studies revealed that binds to both inactive (DFG-out, PDB: 4ASD) active (DFG-in, 3B8R) conformations, significantly stronger affinity state (−107.96 kcal/mol) than (−33.56 kcal/mol), suggesting kinase Functionally, VEGF-induced migration, tube formation, microvessel sprouting vitro ex vivo rat aortic ring assays. reduced tumor-associated formation breast (MDA-MB-231), indicating suppress VEGF-dependent These findings suggest is promising selective agent therapeutic applications angiogenesis-related diseases cancer.

Language: Английский

Strategies to improve the EPR effect: A mechanistic perspective and clinical translation DOI
Mayumi Ikeda, Liwen Wang, Danika Rodrigues

et al.

Journal of Controlled Release, Journal Year: 2022, Volume and Issue: 345, P. 512 - 536

Published: March 23, 2022

Language: Английский

Citations

183
The role of VEGF in cancer-induced angiogenesis and research progress of drugs targeting VEGF DOI Creative Commons

Seyedehdelaram Ghalehbandi,

Jale Yüzügülen, Md Zahidul Islam Pranjol

et al.

European Journal of Pharmacology, Journal Year: 2023, Volume and Issue: 949, P. 175586 - 175586

Published: March 9, 2023

Angiogenesis is a double-edged sword; it mechanism that defines the boundary between health and disease. In spite of its central role in physiological homeostasis, provides oxygen nutrition needed by tumor cells to proceed from dormancy if pro-angiogenic factors tip balance favor angiogenesis. Among factors, vascular endothelial growth factor (VEGF) prominent target therapeutic methods due strategic involvement formation anomalous vasculature. addition, VEGF exhibits immune-regulatory properties which suppress immune cell antitumor activity. signaling through receptors an integral part tumoral angiogenic approaches. A wide variety medicines have been designed ligands this superfamily. Herein, we summarize direct indirect molecular mechanisms demonstrate versatile context cancer angiogenesis current transformative VEGF-targeted strategies interfering with growth.

Language: Английский

Citations

140
Exploring the crosstalk between endothelial cells, immune cells, and immune checkpoints in the tumor microenvironment: new insights and therapeutic implications DOI Creative Commons

Jian-Wen Fang,

Yue Lu,

Jingyan Zheng

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(9)

Published: Sept. 4, 2023

Abstract The tumor microenvironment (TME) is a highly intricate milieu, comprising multitude of components, including immune cells and stromal cells, that exert profound influence on initiation progression. Within the TME, angiogenesis predominantly orchestrated by endothelial (ECs), which foster proliferation metastasis malignant cells. interplay between with ECs complex can either bolster or hinder system. Thus, comprehensive understanding crosstalk essential to advance development immunotherapeutic interventions. Despite recent progress, underlying molecular mechanisms govern remain elusive. Nevertheless, immunomodulatory function has emerged as pivotal determinant response. In light this, study relationship checkpoints garnered considerable attention in field immunotherapy. By targeting specific pathways signaling molecules associated novel strategies may be devised enhance efficacy current treatments. this vein, we sought elucidate ECs, ultimate goal identifying therapeutic targets charting new avenues for

Language: Английский

Citations

87
Green synthesis of gold nanoparticles via Capsicum annum fruit extract: Characterization, antiangiogenic, antioxidant and anti-inflammatory activities DOI Creative Commons

Tejaswini P. Patil,

Anuja Vibhute,

Snehal L. Patil

et al.

Applied Surface Science Advances, Journal Year: 2023, Volume and Issue: 13, P. 100372 - 100372

Published: Jan. 18, 2023

Biological synthesis of gold nanoparticles (AuNPs) is gaining attention researchers because their varieties biomedical applications. This study reported the novel, eco-friendly AuNPs using dried fruit extract Capsicum annum (C. annum). Biosynthesized (Ca-AuNPs) showed UV absorption peak at 540 nm and were found to be stable for up three months. The further characterized by Transmission Electron Microscopy (TEM), Fourier Transform Infrared (FT-IR), Energy Dispersive X-ray Analysis (EDAX) diffraction (XRD) analysis. spherical in shape with size range 20–30 zeta potential confirmed surface charge -26.5 mV. Ca-AuNPs tested anti-angiogenic activity Chorioallantoic membrane (CAM) assay that implied a significant efficiency 100 µg/mL concentration. antioxidant studied 2,2- diphenyl-1-picrylhydrazyl (DPPH) was 86.0% radical scavenging activity. These also revealed anti-inflammatory concentration 100–1200 IC-50 value619.4 µg/mL. present includes phytoconstituents plant material as reducing agents efficiently exploit applications nanoparticles.

Language: Английский

Citations

62
VEGF signaling: Role in angiogenesis and beyond DOI
Pallab Shaw, Shailendra Kumar Dhar Dwivedi, Resham Bhattacharya

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(2), P. 189079 - 189079

Published: Jan. 26, 2024

Language: Английский

Citations

58
Reshaping of the tumor microenvironment by cellular senescence: An opportunity for senotherapies DOI Creative Commons

Mariantonietta D’Ambrosio,

Jesús Gil

Developmental Cell, Journal Year: 2023, Volume and Issue: 58(12), P. 1007 - 1021

Published: June 1, 2023

Language: Английский

Citations

44
Adhesion, metastasis, and inhibition of cancer cells: a comprehensive review DOI Creative Commons
Josef Yayan,

Karl-Josef Franke,

Melanie Berger

et al.

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 51(1)

Published: Jan. 22, 2024

Abstract This comprehensive review delves into cancer’s complexity, focusing on adhesion, metastasis, and inhibition. It explores the pivotal role of these factors in disease progression therapeutic strategies. covers cancer cell migration, invasion, colonization distant organs, emphasizing significance adhesion intricate metastasis process. Inhibition approaches targeting molecules, such as integrins cadherins, are discussed. Overall, this contributes significantly to advancing research developing targeted therapies, holding promise for improving patient outcomes worldwide. Exploring different inhibition strategies revealed promising targets alleviate cells. The effectiveness integrin-blocking antibodies, small molecule inhibitors Focal kinase (FAK) Transforming Growth Factor β (TGF-β) pathway, combination therapies underscores their potential disrupt focal adhesions control epithelial-mesenchymal transition processes. identification FAK, Src, β-catenin SMAD4 offers valuable starting points further development therapies. complex interrelationships between metastatic signaling networks will be relevant new treatment approaches.

Language: Английский

Citations

29
PIK3CA mutation as an acquired resistance driver to EGFR-TKIs in non-small cell lung cancer: Clinical challenges and opportunities DOI Creative Commons
Xiaohong Liu,

Wuxuan Mei,

Pengfei Zhang

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 202, P. 107123 - 107123

Published: March 2, 2024

Epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have significantly enhanced the treatment outcomes in non-small cell lung cancer (NSCLC) patients harboring EGFR mutations. However, occurrence of acquired resistance to EGFR-TKIs is an unavoidable outcome observed these patients. Disruption PI3K/AKT/mTOR signaling pathway can contribute emergence TKIs cancer. The PIK3CA mutations following with lead against EGFR-TKIs. This review provides overview current perspectives regarding involvement development Furthermore, we outline state-of-the-art therapeutic strategies targeting We highlight role mutation as mechanism EGFR-mutant NSCLC. Crucially, explore PIK3CA-mediated cancer, aiming optimize effectiveness treatment.

Language: Английский

Citations

18
Role of Angiogenesis and Its Biomarkers in Development of Targeted Tumor Therapies DOI Creative Commons
Anchal Pathak, Ajay Kumar Pal, Subhadeep Roy

et al.

Stem Cells International, Journal Year: 2024, Volume and Issue: 2024(1)

Published: Jan. 1, 2024

Angiogenesis plays a significant role in the human body, from wound healing to tumor progression. "Angiogenic switch" indicates time-restricted event where imbalance between pro- and antiangiogenic factors results transition prevascular hyperplasia outgrowing vascularized tumor, which eventually leads malignant cancer In last decade, molecular players, i.e., angiogenic biomarkers underlying pathways involved tumorigenesis, have been intensely investigated. Disrupting initiation halting progression of angiogenesis by targeting these has considered as potential treatment approach for angiogenesis. This review discusses currently known available therapies cancer, monoclonal antibodies, aptamers, small inhibitors, miRNAs, siRNAs, angiostatin, endostatin, melatonin analogues, either approved U.S. Food Drug Administration or under clinical preclinical investigations.

Language: Английский

Citations

17
Tumor microenvironment targeted nano-drug delivery systems for multidrug resistant tumor therapy DOI Creative Commons

Xinyue Shao,

Xiaoling Zhao, Binghao Wang

et al.

Theranostics, Journal Year: 2025, Volume and Issue: 15(5), P. 1689 - 1714

Published: Jan. 2, 2025

In recent years, nano-drug delivery systems (Nano-DDS) that target the tumor microenvironment (TME) to overcome multidrug resistance (MDR) have become a research hotspot in field of cancer therapy. By precisely targeting TME and regulating its unique pathological features, such as hypoxia, weakly acidic pH, abnormally expressed proteins, etc., these Nano-DDS enable effective therapeutic agents reversal MDR. This scientific community is increasing investment development diversified exploring their anti-drug potential. Therefore, it particularly important conduct comprehensive review progress TME-targeted years. After brief introduction MDR, design principle structure liposomes, polymer micelles inorganic nanocarriers are focused on, characteristics described. It also demonstrates how break through MDR treatment various mechanisms, discusses synthetic innovation, results overcoming mechanisms. The was concluded with deliberations on key challenges future outlooks

Language: Английский

Citations

4