The tumor microenvironment (TME) is a heterogenous assemblage of malignant and non-malignant cells, including infiltrating immune cells and other stromal cells, together with extracellular matrix and a variety of soluble factors. This complex and dynamic milieu strongly affects tumor differentiation, progression, immune evasion, and response to therapy, thus being an important therapeutic target. The phenotypic and functional features of the various cell types present in the TME are largely dependent on their ability to adopt different metabolic programs. Hence, modulating the metabolism of the cells in the TME, and their metabolic crosstalk, has emerged as a promising strategy in the context of anticancer therapies. Natural compounds offer an attractive tool in this respect as their multiple biological activities can potentially be harnessed to '(re)-educate' TME cells towards antitumoral roles. The present review discusses how natural compounds shape the metabolism of stromal cells in the TME and how this may impact tumor development and progression.
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http://dx.doi.org/10.3390/molecules26123494 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Zhejiang Key Laboratory of Biology and Ecological Regulation of Crop Pathogens and Insects, Institute of Insect Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
The harlequin ladybird, , is a predatory beetle used globally to control pests such as aphids and scale insects. Originating from East Asia, this species has become highly invasive since its introduction in the late 19th century to Europe and North America, posing a threat to local biodiversity. Intraguild predation is hypothesized to drive the success of this invasive species, but the underlying mechanisms remain unknown.
View Article and Find Full Text PDFACS Chem Neurosci
January 2025
Department of Bioengineering and Biotechnology, Birla Institute of Technology Mesra, Ranchi, Jharkhand 835215, India.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, extracellular amyloid-β (Aβ) plaque accumulation, and intracellular neurofibrillary tangles. Recent efforts to find effective therapies have increased interest in natural compounds with multifaceted effects on AD pathology. This study explores natural compounds for their potential to mitigate AD pathology using molecular docking, ADME screening, and assays, with ruscogenin─a steroidal sapogenin from emerging as a promising candidate.
View Article and Find Full Text PDFNatural killer (NK) cells have proven to be safe and effective immunotherapies, associated with favorable treatment responses in chronic myeloid leukemia (CML). Augmenting NK cell function with oncological drugs could improve NK cell-based immunotherapies. Here, we used a high-throughput drug screen consisting of over 500 small-molecule compounds to systematically evaluate the effects of oncological drugs on primary NK cells against CML cells.
View Article and Find Full Text PDFJ Med Chem
January 2025
State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
MTDH-SND1 protein-protein interaction (PPI) plays an important role in the initiation and development of tumors, and it is a target for the treatment of breast cancer. In this study, we identified and synthesized a series of novel small-molecule inhibitors of MTDH-SND1 PPI. The representative compound showed potent activity against MTDH-SND1 PPI with an IC of 487 ± 99 nM and tight binding to the SND1-purified protein with a value of 279 ± 17 nM.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Department of Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Older individuals experience increased susceptibility and mortality to bacterial infections, but the underlying etiology remains unclear. Herein, it is shown that aging-associated reduction of commensal Parabacteroides goldsteinii (P. goldsteinii) in both aged mice and humans critically contributes to worse outcomes of bacterial infection.
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