Novel dual responsive embelin functionalised ZnO nanomaterials amplify DNA damage and induce apoptosis via pERK1/2/p53 pathway in pancreatic ductal adenocarcinoma

Article

作者: Meghana, P ; Ravindranath, B S ; Pradeepa, K ; Rajaput, Pooja S ; Sharath, R ; Sandeep Kumar Jain, R ; Kumaraswamy, H M ; Hari Krishna, R ; Satyanarayan, N D ; Prashanth, N ; Raja Naika, H

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor prognosis and chemoresistance. Nano-bioconjugates, due to their enhanced surface-to-volume ratio, offer significant potential in cancer therapy. In this study, we synthesized ZnO nanoparticles (NPs) using solution combustion method and exhibited a particle size range of 20-70 nm as confirmed by TEM analysis. These NPs were conjugated with embelin, a natural benzoquinone compound. Successful conjugation was confirmed using FTIR spectroscopy. Structural and morphological characteristics of the conjugates were confirmed using XRD, SEM, TEM, FTIR, and EDS color mapping. Embelin conjugated ZnO NPs (Emb-ZnO NPs) were evaluated against PDAC cell lines (PANC-1 and MIA PaCa-2). The nanoconjugates showed significant cytotoxicity compared to individual Embelin and ZnO NPs, with IC₅₀ values of 7.05 ± 0.96 μg/ml (PANC-1) and 8.66 ± 1.46 μg/ml (MIA PaCa-2). Emb-ZnO NPs exhibited tumoricidal effects in clonogenic and migration assays. Fluorescent staining revealed disrupted cellular architecture and significant apoptosis. Immunoblot analysis exhibits deregulation of key pathways, including amplified expression of γ-H2AX (88.48 %), indicative of DNA damage. Concurrently, elevated levels of pChk2 (68.07 %), p53 (89.34 %), and caspase-3 (26.67 %) promote Cell cycle halting and programmed cell death triggered by genomic instability. Conversely, reduced pERK1/2 (53.77 %) expression suggested inhibition of the MAPK pathway by Emb-ZnO NPs. Additionally, the formulation inhibited neovascularization in the CAM model, indicating anti-angiogenic potential. Molecular dynamics simulations of p53 and pERK1/2 aligned with in vitro results. In conclusion, Emb-ZnO NPs is a promising therapeutic candidate for PDAC and other cancers.

2025-12-01·FUNCTIONAL & INTEGRATIVE GENOMICS

NSUN7 promotes cervical cancer progression through activation of ErbB signaling pathway

Article

作者: Lu, Ruijiao ; Li, Yuxia ; Feng, Yangchun ; Abuduhailili, Xieyidai

We aimed to investigate the role of NSUN7 in the progression of Cervical Cancer through a combination of bioinformatics analysis and cell and animal culture experiments. We comprehensively assessed the expression levels of NSUN7 in the TCGA and CCLE databases, and explored its correlations with clinicopathological features, immune cell infiltration, DNA damage repair gene function, drug sensitivity, and methylation status. The NSUN7 gene was disrupted through lentiviral infection, and the effects on cell proliferation, invasion, and apoptosis were evaluated using CCK-8 assay, Transwell migration assay, and flow cytometry analysis. Gene enrichment analysis wasidentify the biological pathways associated with NSUN7 and cervical cancer development. Additionally, a xenograft model of cervical cancer was established to assess the in vivo inhibitory effect of NSUN7 and its impact on pathway molecules. The results of both in vitro and in vivo experiments confirmed that silencing the NSUN7 gene significantly inhibited the growth, spread, and metastasis of cervical cancer cells, while promoting apoptosis. TUNEL assay and HE staining further verified the apoptotic effect of NSUN7 on tumor tissues, and KEGG enrichment analysis revealed a significant enrichment of NSUN7 in the ErbB pathway. Silencing of NSUN7 resulted in a significant down-regulation of key ErbB pathway proteins (HER2, STAT5, PI3K/p-PI3K) as demonstrated by quantitative real-time PCR and Western blot. These findings suggest that NSUN7 may affect the biological behavior of cervical cancer cells and promote tumor development by activating the ErbB signaling pathway.

2025-11-01·PHYTOMEDICINE

The extracts of Ardisia elliptica fruit attenuate inflammation in LPS-activated BV2 microglia via JNK, ERK1/2, p38, and NF-κB signaling inhibition

Article

作者: Yang, Meixia ; Ospondpant, Dusadee ; Tsim, Karl Wah Keung ; Gao, Jin ; Dong, Tina Tingxia

BACKGROUND:

Neuroinflammation is a pivotal defense mechanism against brain infections and injury; the dysregulation contributes to neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease, and multiple sclerosis. Ardisia elliptica Thunb. (Primulaceae), known as Ram Yai or Pilangkasa in Thai traditional medicine, has been used to treat diarrhea with fever. However, the potential of A. elliptica fruit to modulate neuroinflammation remains unexplored.

PURPOSE:

This study aimed to investigate the anti-neuroinflammatory properties of A. elliptica fruit extracts in activated microglia as well as their anti-amyloidogenic effects in vitro.

METHODS:

Lipopolysaccharide (LPS), a potent inflammatory stimulus, was used to activate both BV2 microglia, a well-established model of neuroinflammation, and RAW264.7 macrophages. In the inflammatory studies, assays including qRT-PCR, Western blotting, and phagocytic activity were performed. In the amyloidogenic study, thioflavin T and atomic force microscopy assays were conducted.

RESULTS:

A. elliptica fruit was extracted using ethanol and water. The extracts significantly reduced the mRNA and protein expression of IL-1β, TNF-α, and iNOS in LPS-activated BV2 cells and RAW264.7 cells. The 90 % ethanol extract of A. elliptica fruit exhibited greater efficacy compared to 50 % ethanol or water extracts. In addition, A. elliptica fruit extract significantly decreased the phosphorylation of JNK, ERK1/2, p38, and NF-κB, while markedly attenuating excessive phagocytic activity by reducing uptake of fluorescent beads and Aβ_1-42 fibrils in LPS-activated BV2 cells. Notably, the extracts inhibited Aβ_1-42 fibril formation and disassembled preformed fibril aggregates. Embelin was identified as a major bioactive constituent of the extracts, accounting for part of the identified activities.

CONCLUSION:

Our study elucidates the mechanisms by which A. elliptica fruit extract suppresses inflammation through inhibition of JNK, ERK1/2, p38, and NF-kB pathways in LPS-activated microglia. A. elliptica fruit extracts exhibit both anti-inflammatory and anti-amyloidogenic activities, suggesting the potential as a promising multi-target candidate natural product for neuroinflammatory disorders such as AD.

100 项与 Embelin 相关的药物交易

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