Plumbagin Increases Paclitaxel-Induced Cell Death and Overcomes Paclitaxel Resistance in Breast Cancer Cells through ERK-Mediated Apoptosis Induction

Kawiak, Anna; Domachowska, Anna; Łojkowska, Ewa

doi:10.1021/acs.jnatprod.8b00964

Cited by 25 publications

(12 citation statements)

References 37 publications

(80 reference statements)

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“…MDA-MB-468 cells were treated with ChPL (μM) and PTX (nM) at the following fixed combinations: 0.1/0.1; 0.2/1; 0.5/5; 1/10; 2/20. The combination index (CI) was calculated as previously published (Kawiak et al, 2019). Obtained CI values lower than 1 indicate synergistic activity between compounds, whereas CI values higher or equal to 1 indicate antagonistic and additive activity, respectively.…”

Section: Methodsmentioning

confidence: 99%

3-Chloroplumbagin Induces Cell Death in Breast Cancer Cells Through MAPK-Mediated Mcl-1 Inhibition

et al. 2019

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Resistance acquired toward anti-cancer agents is a significant drawback in breast cancer therapy. A key factor contributing to drug resistance is apoptosis suppression associated with the upregulation of anti-apoptotic Bcl-2 family proteins. Specifically, the anti-apoptotic Mcl-1 protein has been shown to play a significant role in drug resistance, making it an important therapeutic target. The present study aimed at determining the antiproliferative activity of 3-chloroplumbagin (ChPL), a naphthoquinone derived from a Dionaea sp., toward breast cancer cells and examining the involvement of Mcl-1 inhibition in ChPL-induced cell death. The results showed that ChPL inhibited breast cancer cell proliferation and induced apoptosis through the intrinsic pathway through down-regulation of anti-apoptotic Bcl-2 family proteins. The induction of apoptosis by ChPL was found to be mediated through MAP kinase signaling inhibition. ChPL inhibited the phosphorylation of MEK and ERK proteins in breast cancer cells, and increased apoptosis induction in cells with reduced ERK expression. Furthermore, ERK silencing decreased the expression of Mcl-1 in ChPL-treated cells. The results of this research indicate that ChPL induces apoptosis in breast cancer cells through MAPK-mediated Mcl-1 inhibition, suggesting further research into its potential in breast cancer treatment.

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Section: Methodsmentioning

confidence: 99%

3-Chloroplumbagin Induces Cell Death in Breast Cancer Cells Through MAPK-Mediated Mcl-1 Inhibition

et al. 2019

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“…In addition, it is closely related to tumor formation. Increased expression of ERK has been detected in a variety of human tumors, − especially in GC. It has been shown that the activation of ERK signaling promotes GC growth and metastasis, so it is the most important pathway in the development of GC .…”

Section: Resultsmentioning

confidence: 99%

Sanggenon C Suppresses Tumorigenesis of Gastric Cancer by Blocking ERK-Drp1-Mediated Mitochondrial Fission

et al. 2022

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Sanggenon C is a flavonoid extracted from the root bark of white mulberry, which is a traditional Chinese medicine with anti-inflammatory, antioxidative, and antitumor pharmacological effects. In this study, sanggenon C was found to inhibit human gastric cancer (GC) cell proliferation and colony formation, induce GC cell cycle arrest in the G0−G1 phase, and promote GC cell apoptosis. Moreover, sanggenon C was found to decrease the level of mitochondrial membrane potential in GC cells and inhibit mitochondrial fission. Mechanistically, RNA sequencing, bioinformatics analysis, and a series of functional analyses confirmed that sanggenon C inhibited mitochondrial fission to induce apoptosis by blocking the extracellular regulated protein kinases (ERK) signaling pathway, and constitutive activation of ERK significantly abrogated these effects. Finally, sanggenon C was found to suppress the growth of tumor xenografts in nude mice without obvious side effects to the vital organs of animals. This study reveals that sanggenon C could be a novel therapeutic strategy for GC treatment.

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“…This drug also inhibits the effects of other factors on the microtubule system and, together with the stable binding of microtubule proteins, eventually induces apoptosis ( Liu et al, 2017a ). In clinical applications, paclitaxel has shown good efficacy in treating non-small cell lung cancer ( Hoang et al, 2012 ), breast cancer ( Manhas et al, 2022 ), gastric cancer ( Tu et al, 2022 ), nasopharyngeal cancer ( Xia et al, 2022 ), ovarian cancer ( Kong et al, 2023 )and cervical cancer ( Yasunaga et al, 2022 ), particularly for drug-resistant tumors ( Song et al, 2018 ; Kawiak et al, 2019 ). Although the therapeutic efficacy of paclitaxel in glioma has been confirmed, its therapeutic mechanism remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of action of paclitaxel for treating glioblastoma based on single-cell RNA sequencing data and network pharmacology

Rao

et al. 2022

Front. Pharmacol.

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Paclitaxel is an herbal active ingredient used in clinical practice that shows anti-tumor effects. However, its biological activity, mechanism, and cancer cell-killing effects remain unknown. Information on the chemical gene interactions of paclitaxel was obtained from the Comparative Toxicogenomics Database, SwishTargetPrediction, Binding DB, and TargetNet databases. Gene expression data were obtained from the GSE4290 dataset. Differential gene analysis, Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology analyses were performed. Gene set enrichment analysis was performed to evaluate disease pathway activation; weighted gene co-expression network analysis with diff analysis was used to identify disease-associated genes, analyze differential genes, and identify drug targets via protein-protein interactions. The Molecular Complex Detection (MCODE) analysis of critical subgroup networks was conducted to identify essential genes affected by paclitaxel, assess crucial cluster gene expression differences in glioma versus standard samples, and perform receiver operator characteristic mapping. To evaluate the pharmacological targets and signaling pathways of paclitaxel in glioblastoma, the single-cell GSE148196 dataset was acquired from the Gene Expression Omnibus database and preprocessed using Seurat software. Based on the single-cell RNA-sequencing dataset, 24 cell clusters were identified, along with marker genes for the two different cell types in each cluster. Correlation analysis revealed that the mechanism of paclitaxel treatment involves effects on neurons. Paclitaxel may affect glioblastoma by improving glucose metabolism and processes involved in modulating immune function in the body.

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Plumbagin Increases Paclitaxel-Induced Cell Death and Overcomes Paclitaxel Resistance in Breast Cancer Cells through ERK-Mediated Apoptosis Induction

Cited by 25 publications

References 37 publications

3-Chloroplumbagin Induces Cell Death in Breast Cancer Cells Through MAPK-Mediated Mcl-1 Inhibition

3-Chloroplumbagin Induces Cell Death in Breast Cancer Cells Through MAPK-Mediated Mcl-1 Inhibition

Sanggenon C Suppresses Tumorigenesis of Gastric Cancer by Blocking ERK-Drp1-Mediated Mitochondrial Fission

Mechanism of action of paclitaxel for treating glioblastoma based on single-cell RNA sequencing data and network pharmacology

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