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Chrysin Encapsulated Copper Nanoparticles with Low Dose of Gamma Radiation Elicit Tumor Cell Death Through p38 MAPK/NF-κB Pathways.

ABSTRACT: Improving radiation effect on tumor cells using radiosensitizers is gaining traction for improving chemoradiotherapy. This study aimed to evaluate copper nanoparticles (CuNPs) synthesized using chrysin as radiosensitizer with γ-radiation on biochemical and histopathological approaches in mice bearing Ehrlich solid tumor. CuNPs were characterized with irregular round sharp shape with size range of 21.19-70.79 nm and plasmon absorption at 273 nm. In vitro study on MCF-7 cells detected cytotoxic effect of CuNPs with IC₅₀ of 57.2 ± 3.1 μg. In vivo study was performed on mice transplanted with Ehrlich solid tumor (EC). Mice were injected with CuNPs (0.67 mg/kg body weight) and/or exposed to low dose of gamma radiation (0.5 Gy). EC mice exposed to combined treatment of CuNPs and radiation showed a marked reduction in tumor volume, ALT and CAT, creatinine, calcium, and GSH, along with elevation in MDA, caspase-3 in parallel with inhibition of NF-κB, p38 MAPK, and cyclin D₁ gene expression. Comparing histopathological findings of treatment groups ends that combined treatment was of higher efficacy, showing tumor tissue regression and increase in apoptotic cells. In conclusion, CuNPs with a low dose of gamma radiation showed more powerful ability for tumor suppression via promoting oxidative state, stimulating apoptosis, and inhibiting proliferation pathway through p38MAPK/NF-κB and cyclinD1.

SUBMITTER: Abdelhakm LO

PROVIDER: S-EPMC10509080 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Chrysin Encapsulated Copper Nanoparticles with Low Dose of Gamma Radiation Elicit Tumor Cell Death Through p38 MAPK/NF-κB Pathways.

Abdelhakm Lubna O LO Kandil Eman I EI Mansour Somaya Z SZ El-Sonbaty Sawsan M SM

Biological trace element research 20230311 11

Improving radiation effect on tumor cells using radiosensitizers is gaining traction for improving chemoradiotherapy. This study aimed to evaluate copper nanoparticles (CuNPs) synthesized using chrysin as radiosensitizer with γ-radiation on biochemical and histopathological approaches in mice bearing Ehrlich solid tumor. CuNPs were characterized with irregular round sharp shape with size range of 21.19-70.79 nm and plasmon absorption at 273 nm. In vitro study on MCF-7 cells detected cytotoxic ef ...[more]

PMID: 36905557

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Project description:BackgroundIntervertebral disc degeneration (IVDD) is a common spine disease with inflammation as its main pathogenesis. Mulberroside A (MA), isolated from herbal medicine, possesses anti-inflammatory characteristics in many diseases. Whereas, there is little exploration of the therapeutic potential of MA on IVDD. This study aimed at the therapeutic potential of MA on IVDD in vivo and in vitro and the mechanism involved.MethodsIn vitro, western blotting, RT-qPCR, and immunofluorescence analysis were implemented to explore the bioactivity of MA on interleukin-1 beta (IL-1β)-induced inflammation nucleus pulposus cells (NPCs) isolated from Sprague-Dawley male rats. In vivo, X-ray and MRI were applied to measure the morphological changes, and histological staining and immunohistochemistry were employed to investigate the histological changes of intervertebral disc sections on puncture-induced IVDD rat models.ResultsIn vitro, MA up-regulated the expression level of anabolic-related proteins (Aggrecan and Collagen II) and decreased catabolic-related proteins (Mmp2, Mmp3, Mmp9, and Mmp13) in IL-1β-induced NPCs. Furthermore, MA inhibits the production of pro-inflammatory factors (Inos, Cox-2, and Il-6) stimulated by IL-1β. Mechanistically, MA inhibited the signal transduction of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) pathways in IL-1β-induced NPCs. Moreover, MA might bind to Ppar-γ and then suppress the NF-kB pathway. In vivo experiment illustrated that MA mitigates the IVDD progression in puncture-induced IVDD model. X-ray and MRI images showed MA restore the disc height and T2-weighted signal intensity after puncturing. H&E and Safranin O/Fast Green also showed MA also alleviated morphological changes caused by acupuncture. In addition, MA reversed the expression level of Mmp13, Aggrecan, Collagen II, and Ppar-γ induced in IVDD models.ConclusionsMA inhibited degenerative phenotypes in NPCs and alleviated IVDD progression via inhibiting the MAPK and NF-κB pathways; besides, MA suppressed the NF-κB pathway was attributed to activating Ppar-γ, those supported that MA or Ppar-γ might be a potential drug or target for IVDD.

Dataset Information

Chrysin Encapsulated Copper Nanoparticles with Low Dose of Gamma Radiation Elicit Tumor Cell Death Through p38 MAPK/NF-κB Pathways.

Publications

Chrysin Encapsulated Copper Nanoparticles with Low Dose of Gamma Radiation Elicit Tumor Cell Death Through p38 MAPK/NF-κB Pathways.

Similar Datasets

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