Salvia chinensis Benth Inhibits Triple-Negative Breast Cancer Progression by Inducing the DNA Damage Pathway

Wang, Kainan; Hu, Ye; Han, Lin-lin; Zhao, Shanshan; Song, Chunyan; Sun, Siwen; Lv, Hui-yun; Jiang, Ni-na; Xv, Ling-zhi; Zhao, Zuo-wei; Li, Man

doi:10.3389/fonc.2022.882784

Cited by 3 publications

(3 citation statements)

References 42 publications

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“… 19 In addition, beta-sitosterol affects several cell signaling pathways, including the cell cycle, proliferation, angiogenesis, apoptosis, and anticancer pathways, especially in TNBC cells. 20 , 21 These findings suggest that these components may be critical for the therapeutic effects of CSSGF.…”

Section: Discussionmentioning

confidence: 89%

Unveiling the Mechanism of the ChaiShao Shugan Formula Against Triple-Negative Breast Cancer

Fan,

Huang,

Liu

et al. 2024

DDDT

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Background:The ChaiShao Shugan Formula (CSSGF) is a traditional Chinese medicine formula with recently identified therapeutic value in triple-negative breast cancer (TNBC). This study aimed to elucidate the underlying mechanism of CSSGF in TNBC treatment. Methods: TNBC targets were analyzed using R and data were from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The major ingredients and related protein targets of CSSGF were explored via the Traditional Chinese Medicine Systems Pharmacology database, and an ingredient-target network was constructed via Cytoscape to identify hub genes. The STRING database was used to construct the PPI network. GO and KEGG enrichment analyses were performed via R to obtain the main targets. The online tool Kaplan-Meier plotter was used to identify the prognostic genes. Molecular docking was applied to the core target genes and active ingredients. MDA-MB-231 and MCF-7 cell lines were used to verify the efficacy of the various drugs. Results: A total of 4562 genes were screened as TNBC target genes. The PPI network consisted of 89 nodes and 845 edges. Our study indicated that quercetin, beta-sitosterol, luteolin and catechin might be the core ingredients of CSSGF, and EGFR and c-Myc might be the latent therapeutic targets of CSSGF in the treatment of TNBC. GO and KEGG analyses indicated that the anticancer effect of CSSGF on TNBC was mainly associated with DNA binding, transcription factor binding, and other biological processes. The related signaling pathways mainly involved the TNF-a, IL-17, and apoptosis pathways. The molecular docking data indicated that quercetin, beta-sitosterol, luteolin, and catechin had high affinity for EGFR, JUN, Caspase-3 and ESR1, respectively. In vitro, we found that CSSGF could suppress the expression of c-Myc or promote the expression of EGFR. In addition, we found that quercetin downregulates c-Myc expression in two BC cell lines. Conclusion:This study revealed the effective ingredients and latent molecular mechanism of action of CSSGF against TNBC and confirmed that quercetin could target c-Myc to induce anti-BC effects.

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Section: Discussionmentioning

confidence: 89%

Unveiling the Mechanism of the ChaiShao Shugan Formula Against Triple-Negative Breast Cancer

Fan,

Huang,

Liu

et al. 2024

DDDT

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“…Compound 5 is a commonly occurring phytosterol called β-sitosterol, which is a key component present in plants. Out of the many pharmacological and biological effects that have been reported for this compound over the past decades, anti-inflammatory, angiogenic, antiadipogenic, anti-diabetic, anti-oxidant, anti-cancer, immunomodulatory activities and a role in cardiovascular diseases prevention can be mentioned, reported from recent findings that can be beneficial in drug developments and other therapeutic applications [45][46][47][48][49][50][51]. The hypocholesterolemic effects of E. hirta and its role in curing obesity have been linked to this natural compound [22], as well as the larvicidal activity of E. thymifolia [21].…”

Section: Discussionmentioning

confidence: 99%

Phytochemical Study of Euphorbia turcomanica Boiss.

et al. 2022

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The attraction to the Euphorbia genus, with its remarkable diversity in species, is due to its variety of chemical compositions. Euphorbia turcomanica is one of the species of the spurge family growing wildly in Iran. This research aims to investigate the presence of secondary metabolites, specially terpenoid compounds, in terms of structural determination. Samples of E. tucomanica were finely powdered and macerated with acetone/dichloromethane 2:1. Repeated column chromatography using silica gel, MPLC, and HPLC methods followed by the analysis of data obtained from spectroscopic means was carried out to purify and identify the terpenoid constituents. The chemical structures of nine known terpenoids were determined for the first time from E. turcomanica during this study. Loliolide (1), a monoterpene, and eight steroids and triterpenes, including simiarenol (2), isomultiflorenol (3), cycloart-25-ene-3β,24-diol (4), β-sitosterol (5), cycloart-23-ene-3β,25-diol (6), 3α, 11α-dihydroxyurs-12-ene (7), 3β, 24β, 25-trihydroxycycloartane (8), and 7α-hydroxystigmasterol (9) were isolated and identified. E. tucomanica, with a rich terpenoid profile, can be one of the valuable and economic sources providing compounds for drug development.

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“…[ 6 ] Furthermore, Wang et al found that SJC aqueous extract inhibits the occurrence and development of triple-negative breast cancer through DNA damage-related pathways. [ 7 ] Various studies have reported the anti-CRC effects of the primary components of Salvia chinensis Benth , such as Ursolic acid, quercetin, and resveratrol. For instance, Ursolic acid has been documented to induce apoptosis and modulate autophagy in apoptosis-resistant CRC cells via the JNK pathway.…”

Section: Introductionmentioning

confidence: 99%

Exploring the pharmacological and molecular mechanisms of Salvia chinensis Benth in colorectal cancer: A network pharmacology and molecular docking study

Zheng,

Wang,

Gao

et al. 2023

Medicine

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While Salvia chinensis Benth (commonly known as “Shijianchuan” in Chinese, and abbreviated as SJC) is commonly used in adjuvant therapy for colorectal cancer (CRC) in traditional Chinese medicine, its mechanism of action remains unclear. In this study, Initially, we examined the impact of SJC on CRC cells in an in vitro setting. Next, we initially retrieved the primary active components and targets of SJC from databases such as TCMSP and existing literature. Subsequently, we integrated differential gene expression data from the GEO database and collected CRC-related targets from resources like DisGeNET. The matching of these datasets enabled the identification of SJC-CRC targets. We constructed a protein-protein interaction network and identified core targets through topological analysis. GO and KEGG enrichment analyses were performed using clusterProfiler. We established networks linking traditional Chinese medicine components to targets and core targets to signaling pathways. Additionally, we performed molecular docking to validate interactions between the main compounds and targets, and employed Western blot analysis to explore how the major components of SJC affect crucial signaling pathways. In this study, SJC inhibited the viability of HCT-116 and HT-29 cells. We identified a total of 11 active components in SJC along with 317 target genes. Among these, there were 8612 target genes associated with CRC, and we successfully matched 276 SJC-CRC target genes. Through topological analysis of the protein-protein interaction network, we pinpointed 20 core targets. It was revealed that SJC effects are linked to genes governing processes like cell apoptosis, proliferation, hypoxia, oxidative stress, and signaling pathways such as PI3K-Akt through GO and KEGG pathway enrichment analyses. Additionally, we applied molecular docking techniques and observed that the majority of active compounds displayed robust binding affinity with the selected targets. In vitro experiments suggested that SJC and its key component, Ursolic acid, may exert its anti-CRC effects by modulating the core PI3K/AKT signaling pathway through inhibiting the phosphorylation of the target Akt1. This discovery is consistent with the predictions derived from network pharmacology methods. This study marks the inaugural utilization of bioinformatics methods in conjunction with in vitro experiments to comprehensively investigate the pharmacological and molecular mechanisms responsible for SJC anti-CRC effects.

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Salvia chinensis Benth Inhibits Triple-Negative Breast Cancer Progression by Inducing the DNA Damage Pathway

Cited by 3 publications

References 42 publications

Unveiling the Mechanism of the ChaiShao Shugan Formula Against Triple-Negative Breast Cancer

Unveiling the Mechanism of the ChaiShao Shugan Formula Against Triple-Negative Breast Cancer

Phytochemical Study of Euphorbia turcomanica Boiss.

Exploring the pharmacological and molecular mechanisms of Salvia chinensis Benth in colorectal cancer: A network pharmacology and molecular docking study

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