Bruceine D Identified as a Drug Candidate against Breast Cancer by a Novel Drug Selection Pipeline and Cell Viability Assay

Cipriani, Claudia; Pacheco, Maria Pires; Kishk, Ali; Wachich, Maryem; Abankwa, Daniel; Schaffner-Reckinger, Elisabeth; Sauter, Thomas

doi:10.3390/ph15020179

Cited by 5 publications

(1 citation statement)

References 86 publications

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“…Increasing findings support the use of Narciclasine and Bruceine D as antitumor agents [33,46]. Several studies have reported the antitumor mechanisms of the two drugs [47][48][49], but natural products often have multiple molecular targets.…”

Section: Discussionmentioning

confidence: 92%

Bruceine D and Narclasine inhibit the proliferation of breast cancer cells and the prediction of potential drug targets

Chen,

2024

PLoS ONE

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Background Breast cancer is one of the most common female malignancies. This study explored the underlying mechanism through which the two plant compounds (Brucaine D and Narclasine) inhibited the proliferation of breast cancer cells. Objective The purpose of this study was to explore the effect of Brucaine D and Narclasine on breast cancer development and their potential drug targets. Methods GSE85871 dataset containing 212 samples and the hallmark gene set “h.all.v2023.1.Hs.symbols.gmt” were downloaded from the Gene Expression Omnibus (GEO) database and the Molecular Signatures Database (MSigDB) database, respectively. Principal component analysis (PCA) was applied to classify clusters showing similar gene expression pattern. Single sample gene set enrichment analysis (ssGSEA) was used to calculate the hallmark score for different drug treatment groups. The expressions of genes related to angiogenesis, glycolysis and cell cycle were detected. Protein-protein interaction (PPI) network analysis was performed to study the interaction of the hub genes. Then, HERB database was employed to identify potential target genes for Narclasine and Bruceine D. Finally, in vitro experiments were conducted to validate partial drug-target pair. Results PCA analysis showed that the significant changes in gene expression patterns took place in 6 drugs treatment groups (Narciclasine, Bruceine D, Japonicone A, 1beta-hydroxyalatolactone, Britanin, and four mixture drugs) in comparison to the remaining drug treatment groups. The ssGSEA pathway enrichment analysis demonstrated that Narciclasine and Bruceine treatments had similar enriched pathways, for instance, suppressed pathways related to angiogenesis, Glycolysis, and cell cycle, etc.. Further gene expression analysis confirmed that Narciclasine and Bruceine had a strong ability to inhibit these cell cycle genes, and that MYC, CHEK2, MELK, CDK4 and EZH2 were closely interacted with each other in the PPI analysis. Drug target prediction revealed that Androgen Receptor (AR) and Estrogen Receptor 1 (ESR1) were the targets for Bruceine D, and Cytochrome P450 3A4 enzyme (CYP3A4) was the target for Narciclasine. Cell experiments also confirmed the connections between Narciclasine and CYP3A4. Conclusion The present study uncovered that Narciclasine and Bruceine D could inhibit the growth of breast cancer and also predicted the potential targets for these two drugs, providing a new therapeutic direction for breast cancer patients.

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Section: Discussionmentioning

confidence: 92%

Bruceine D and Narclasine inhibit the proliferation of breast cancer cells and the prediction of potential drug targets

Chen,

2024

PLoS ONE

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Review on the pharmacological effects and pharmacokinetics of scutellarein

Lai,

2024

Archiv der Pharmazie

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Scutellarein is a flavonoid from Scutellaria baicalensis Georgi that has been shown to have a variety of pharmacological activities. This review aims to summarize the pharmacological and pharmacokinetic studies on scutellarein and provide useful information for relevant scholars. Pharmacological studies indicate that scutellarein possesses a diverse range of pharmacological properties, including but not limited to anti‐inflammatory, antioxidant, antiviral, neuroprotective, hypoglycemic, hypolipidemic, anticancer, and cardiovascular protective effects. Further investigation reveals that the pharmacological effects of scutellarein are driven by multiple mechanisms. These mechanisms encompass the scavenging of free radicals, inhibition of the activation of inflammatory signaling pathways and expression of inflammatory mediators, inhibition of the activity of crucial viral proteins, suppression of gluconeogenesis, amelioration of insulin resistance, improvement of cerebral ischemia‐reperfusion injury, induction of apoptosis in cancer cells, and prevention of myocardial hypertrophy, among others. In summary, these pharmacological studies suggest that scutellarein holds promise for the treatment of various diseases. It is imperative to conduct clinical studies to further elucidate the therapeutic effects of scutellarein. However, it is worth noting that studies on the pharmacokinetics reveal an inhibitory effect of scutellarein on uridine 5′‐diphosphate glucuronide transferases and cytochrome P450 enzymes, potentially posing safety risks.

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Exploring pharmacological active ingredients of traditional Chinese medicine by pharmacotranscriptomic map in ITCM

Tian

ZHANG

Yuan

et al. 2023

Briefings in Bioinformatics

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With the emergence of high-throughput technologies, computational screening based on gene expression profiles has become one of the most effective methods for drug discovery. More importantly, profile-based approaches remarkably enhance novel drug–disease pair discovery without relying on drug- or disease-specific prior knowledge, which has been widely used in modern medicine. However, profile-based systematic screening of active ingredients of traditional Chinese medicine (TCM) has been scarcely performed due to inadequate pharmacotranscriptomic data. Here, we develop the largest-to-date online TCM active ingredients-based pharmacotranscriptomic platform integrated traditional Chinese medicine (ITCM) for the effective screening of active ingredients. First, we performed unified high-throughput experiments and constructed the largest data repository of 496 representative active ingredients, which was five times larger than the previous one built by our team. The transcriptome-based multi-scale analysis was also performed to elucidate their mechanism. Then, we developed six state-of-art signature search methods to screen active ingredients and determine the optimal signature size for all methods. Moreover, we integrated them into a screening strategy, TCM-Query, to identify the potential active ingredients for the special disease. In addition, we also comprehensively collected the TCM-related resource by literature mining. Finally, we applied ITCM to an active ingredient bavachinin, and two diseases, including prostate cancer and COVID-19, to demonstrate the power of drug discovery. ITCM was aimed to comprehensively explore the active ingredients of TCM and boost studies of pharmacological action and drug discovery. ITCM is available at http://itcm.biotcm.net.

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Bruceine D Identified as a Drug Candidate against Breast Cancer by a Novel Drug Selection Pipeline and Cell Viability Assay

Cited by 5 publications

References 86 publications

Bruceine D and Narclasine inhibit the proliferation of breast cancer cells and the prediction of potential drug targets

Bruceine D and Narclasine inhibit the proliferation of breast cancer cells and the prediction of potential drug targets

Review on the pharmacological effects and pharmacokinetics of scutellarein

Exploring pharmacological active ingredients of traditional Chinese medicine by pharmacotranscriptomic map in ITCM

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