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

Current status and advances of immunotherapy in nasopharyngeal carcinoma DOI Creative Commons

Jianying Xu,

Xiaoli Wei, Yiqin Wang

et al.

Therapeutic Advances in Medical Oncology, Journal Year: 2022, Volume and Issue: 14

Published: Jan. 1, 2022

The general immune landscape of nasopharyngeal carcinoma (NPC) renders immunotherapy suitable for patients with NPC. Immune checkpoint inhibitors (ICIs) based on programmed death-1/programmed death ligand-1 (PD-1/PD-L1) blockade have made a breakthrough the approval PD-1 inhibitor refractory recurrence and/or metastatic (R/M NPC) and in combination gemcitabine cisplatin as first line R/M NPC 2021 China. incorporation ICIs into treatment paradigms has become clinical hot spot many prospective studies are ongoing. In this review, we provide comprehensive overview rationale current status, advances challenges published data, ongoing trials. We focus application monotherapy its chemotherapy summarize explorations other approaches, example, PD-1/PD-L1 antiangiogenic molecular targeted agents, cancer vaccines, adaptive immunotherapy, new ICI agents beyond also describe studies' status ICIs-based immunomodulatory strategies local advanced pay attention to biomarker personalized hope insights practice future studies.

Language: Английский

Citations

52
Antispasmodic activity of carnosic acid extracted from rosmarinus officinalis: Isolation, spectroscopic characterization, DFT studies, and in silico molecular docking investigations DOI
Kun Wei, Hitler Louis, Wilfred Emori

et al.

Journal of Molecular Structure, Journal Year: 2022, Volume and Issue: 1260, P. 132795 - 132795

Published: March 9, 2022

Language: Английский

Citations

51
Ferulic Acid: A Natural Phenol That Inhibits Neoplastic Events through Modulation of Oncogenic Signaling DOI Creative Commons
Hardeep Singh Tuli, Ajay Kumar, Seema Ramniwas

et al.

Molecules, Journal Year: 2022, Volume and Issue: 27(21), P. 7653 - 7653

Published: Nov. 7, 2022

Despite the immense therapeutic advances in field of health sciences, cancer is still to be found among global leading causes morbidity and mortality. Ethnomedicinally, natural bioactive compounds isolated from various plant sources have been used for treatment several types gained notable attention. Ferulic acid, a compound derived seeds, nuts, leaves, fruits, exhibits variety pharmacological effects cancer, including its proapoptotic, cell-cycle-arresting, anti-metastatic, anti-inflammatory activities. This review study presents thorough overview molecular targets cellular signaling pathways modulated by ferulic acid diverse malignancies, showing high potential this phenolic developed as candidate agent novel anticancer therapeutics. In addition, current investigations develop promising synergistic formulations are also discussed.

Language: Английский

Citations

43
The Role of Inflammation and Therapeutic Concepts in Diabetic Retinopathy—A Short Review DOI Open Access
Krzysztof Gomułka,

Michał Ruta

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1024 - 1024

Published: Jan. 5, 2023

Diabetic retinopathy (DR) as a microangiopathy is the most common complication in patients with diabetes mellitus (DM) and remains leading cause of blindness among adult population. DM its complicated pathomechanism relates to chronic hyperglycemia, hypoinsulinemia, dyslipidemia hypertension—all these components molecular pathways maintain oxidative stress, formation advanced glycation end-products, microvascular changes, inflammation, retinal neurodegeneration one key players diabetes-associated perturbations. In this current review, we discuss natural history DR special emphasis on ongoing inflammation role vascular endothelial growth factor (VEGF). Additionally, provide an overview principles diabetic treatments, i.e., laser therapy, anti-VEGF steroid options.

Language: Английский

Citations

39
Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond DOI Creative Commons
Samar Al Bitar,

Marwan El‐Sabban,

Samer Doughan

et al.

World Journal of Gastroenterology, Journal Year: 2023, Volume and Issue: 29(9), P. 1395 - 1426

Published: March 7, 2023

Colorectal cancer (CRC) is the third most diagnosed malignancy and a major leading cause of cancer-related deaths worldwide. Despite advances in therapeutic regimens, number patients presenting with metastatic CRC (mCRC) increasing due to resistance therapy, conferred by small population cells, known as stem cells. Targeted therapies have been highly successful prolonging overall survival mCRC. Agents are being developed target key molecules involved drug-resistance metastasis CRC, these include vascular endothelial growth factor, epidermal factor receptor, human receptor-2, mitogen-activated extracellular signal-regulated kinase, addition immune checkpoints. Currently, there several ongoing clinical trials newly targeted agents, which shown considerable efficacy improved prognosis who do not benefit from conventional chemotherapy. In this review, we highlight recent developments use existing novel agents against drug-resistant Furthermore, discuss limitations challenges associated therapy strategies combat intrinsic acquired therapies, importance implementing better preclinical models application personalized based on predictive biomarkers for treatment selection.

Language: Английский

Citations

37
Roles of TGF-β signals in tumor microenvironment via regulation of the formation and plasticity of vascular system DOI Creative Commons
Tetsuro Watabe, Kazuki Takahashi, Kristian Pietras

et al.

Seminars in Cancer Biology, Journal Year: 2023, Volume and Issue: 92, P. 130 - 138

Published: April 15, 2023

Language: Английский

Citations

33
Inhibiting Angiogenesis by Anti-Cancer Saponins: From Phytochemistry to Cellular Signaling Pathways DOI Creative Commons
Mohammad Bagher Majnooni, Sajad Fakhri, Mustafa Ghanadian

et al.

Metabolites, Journal Year: 2023, Volume and Issue: 13(3), P. 323 - 323

Published: Feb. 22, 2023

Saponins are one of the broadest classes high-molecular-weight natural compounds, consisting mainly a non-polar moiety with 27 to 30 carbons and polar containing sugars attached sapogenin structure. found in more than 100 plant families as well marine organisms. have several therapeutic effects, including their administration treatment various cancers. These compounds also reveal noteworthy anti-angiogenesis effects critical strategies for inhibiting cancer growth metastasis. In this study, comprehensive review is performed on electronic databases, PubMed, Scopus, ScienceDirect, ProQuest. Accordingly, structural characteristics triterpenoid/steroid saponins anti-cancer were highlighted, focusing anti-angiogenic related mechanisms. Consequently, saponins, expression genes vascular endothelial factor (VEGF) hypoxia-inducible 1-α (HIF-1α) two main mechanisms triterpenoid steroidal saponins. The inhibition inflammatory signaling pathways that stimulate angiogenesis, such pro-inflammatory cytokines, mitogen-activated protein kinase (MAPKs), phosphoinositide 3-kinases/protein B (PI3K/Akt), other Furthermore, activity was closely binding site sugar moiety, type number monosaccharide units, presence some functional groups aglycone Therefore, suitable candidates by which extensive pre-clinical clinical trial studies recommended.

Language: Английский

Citations

25
Regulation of VEGF-A expression and VEGF-A-targeted therapy in malignant tumors DOI Creative Commons

Yan Kang,

Huiting Li,

Liu Yi-ping

et al.

Journal of Cancer Research and Clinical Oncology, Journal Year: 2024, Volume and Issue: 150(5)

Published: April 30, 2024

Vascular endothelial growth factor A (VEGF-A), a highly conserved dimeric glycoprotein, is key regulatory gene and marker molecule of angiogenesis. The upregulation VEGF-A facilitates the process tumor vascularization, thereby fostering initiation progression malignant neoplasms. Many genes can adjust angiogenesis tumors by changing expression VEGF-A. In addition, also exhibits immune properties, which directly or indirectly suppresses antitumor activity cells. emergence VEGF-A-targeted therapy alone in rational combinations has revolutionized treatment various cancers. This review discusses how diverse mechanisms regulate to promote role microenvironment. application drugs targeting summarized including antibody traditional Chinese medicine.

Language: Английский

Citations

16
Natural-product-based, carrier-free, noncovalent nanoparticles for tumor chemo-photodynamic combination therapy DOI Creative Commons
Zhonglei Wang, Liyan Yang

Pharmacological Research, Journal Year: 2024, Volume and Issue: 203, P. 107150 - 107150

Published: March 21, 2024

Cancer, with its diversity, heterogeneity, and complexity, is a significant contributor to global morbidity, disability, mortality, highlighting the necessity for transformative treatment approaches. Photodynamic therapy (PDT) has aroused continuous interest as viable alternative conventional cancer treatments that encounter drug resistance. Nanotechnology brought new advances in medicine shown great potential delivery treatment. For precise efficient therapeutic utilization of such tumor approach high spatiotemporal selectivity minimal invasiveness, carrier-free noncovalent nanoparticles (NPs) based on chemo-photodynamic combination essential. Utilizing natural products foundation nanodrug development offers unparalleled advantages, including exceptional pharmacological activity, easy functionalization/modification, well biocompatibility. The natural-product-based, carrier-free, NPs revealed excellent synergistic anticancer activity comparison free photosensitizers bioactive products, representing an favorable avenue improve efficacy. Herein, comprehensive summary current strategies representative application examples past decade (such paclitaxel, 10-hydroxycamptothecin, doxorubicin, etoposide, combretastatin A4, epigallocatechin gallate, curcumin) therapy. We highlight insightful design synthesis smart aim enhance PDT Meanwhile, we discuss future challenges opportunities associated these provide enlightenment, spur innovative ideas, facilitate PDT-mediated clinical transformation.

Language: Английский

Citations

15
Synergistic therapeutic strategies and engineered nanoparticles for anti-vascular endothelial growth factor therapy in cancer DOI
Asmaa F. Khafaga, Mohamed M. S. Gaballa, Reham Karam

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 341, P. 122499 - 122499

Published: Feb. 10, 2024

Language: Английский

Citations

12