Virtual screening of the multi-gene regulatory molecular mechanism of Si-Wu-tang against non-triple-negative breast cancer based on network pharmacology combined with experimental validation

2021 ◽  
Vol 269 ◽  
pp. 113696
Author(s):  
Zeye Zhang ◽  
Jia Liu ◽  
Yifan Liu ◽  
Danning Shi ◽  
Yueshuang He ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Virtual Screening ◽  
Molecular Mechanism ◽  
Triple Negative Breast Cancer ◽  
Experimental Validation ◽  
Triple Negative ◽  
Network Pharmacology ◽  
Gene Regulatory

scholarly journals Cordycepin Combined with Doxorubicin Inhibits Triple-negative Breast Cancer by TNF Signaling Pathways

2021 ◽  
Author(s):  
Haichen Huang ◽  
Wenya Wu ◽  
Xiaomin Li ◽  
Chengyi Liu ◽  
Xiaoping Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Docking ◽  
Side Effects ◽  
Molecular Mechanism ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
The Body ◽  
Network Pharmacology ◽  
Control Group ◽  
Xenograft Tumor

Abstract Background: Triple negative breast cancer (TNBC) is a subtype of breast cancer with high mortality and poor prognosis. This study was designed to explore the effect of cordycepin combined with doxorubicin against TNBC, and then explore the molecular mechanism of this process.Methods: First of all, the effect of the combination of drugs on xenograft tumor and liver of mice was carried out to study the effect of combined drug on TNBC and its toxic effect on the body. Relevant genes are obtained through the GenBank and intersected, then the molecular mechanism is explored through GO, KEGG analysis，PPI network construction and other network pharmacological methods. The results of Network pharmacology through molecular docking, immunohistochemistry and other biological experiments to verify. Results: The results show that the combination of drugs can significantly affect the size and weight of the xenograft tumor. The tumor weight of the control group is 3.57 times that of the combined group, and the effect is more obvious than that of the single medication. The liver status, liver index, AST and ALT index of mice were not significantly different (P>0.05), indicating that the combination of drugs has no obvious toxic and side effects on the body. Through the above-mentioned series of network pharmacology methods, the final results we obtained focused on the TNF pathway and TNF-related targets such as MAP3K7, NFKB1, MAPK8 and so on.The results of molecular docking and biological verification were consistent with those of network pharmacology. Conclusions: Cordycepin combined with doxorubicin can inhibit the growth of TNBC without obvious toxicity. The main molecular mechanism of action is to target and regulate the TNF pathway. This provides a new direction for clinical treatment of TNBC, which can effectively treat triple negative breast cancer and reduce the side effects of drugs.

Machine Learning-based Virtual Screening Strategy Reveals Some Natural Compounds As Potential PAK4 Inhibitors In Triple Negative Breast Cancer

2020 ◽  
Vol 18 ◽  
Author(s):  
Opeyemi Iwaloye ◽  
Olusola Olalekan Elekofehinti ◽  
Babatomiwa Kikiowo ◽  
Emmanuel Ayo Oluwarotimi ◽  
Toyin Mary Fadipe
Keyword(s):  
Breast Cancer ◽  
Virtual Screening ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Binding Free Energy ◽  
Natural Compounds ◽  
Energy Calculation ◽  
Reference Drug ◽  
Predictive Quality

Background: P-21 activating kinase 4 (PAK4) is implicated in poor prognosis of many cancers, especially in the progression of Triple Negative Breast Cancer (TNBC). The present study was aimed at designing some potential drug candidates as PAK4 inhibitors for breast cancer therapy. Objective: This study aimed to finding novel inhibitors of PAK4 from natural compounds using computational approach. Methods: An e-pharmacophore model was developed from docked PAK4-coligand complex and used to screen over a thousand natural compounds downloaded from BIOFACQUIM and NPASS databases to match a minimum of 5 sites for selected (ADDDHRR) hypothesis. The robustness of the virtual screening method was accessed by well-established methods including EF, ROC, BEDROC, AUAC, and the RIE. Compounds with fitness score greater than one were filtered by applying molecular docking (HTVS, SP, XP and Induced fit docking) and ADME prediction. Using Machine learningbased approach QSAR model was generated using Automated QSAR. The computed top model kpls_des_17 (R2= 0.8028, RMSE = 0.4884 and Q2 = 0.7661) was used to predict the pIC50 of the lead compounds. Internal and external validations were accessed to determine the predictive quality of the model. Finally the binding free energy calculation was computed. Results: The robustness/predictive quality of the models were affirmed. The hits had better binding affinity than the reference drug and interacted with key amino acids for PAK4 inhibition. Overall, the present analysis yielded three potential inhibitors that are predicted to bind with PAK4 better than reference drug tamoxifen. The three potent novel inhibitors vitexin, emodin and ziganein recorded IFD score of -621.97 kcal/mol, -616.31 kcal/mol and -614.95 kcal/mol, respectively while showing moderation for ADME properties and inhibition constant. Conclusion: It is expected that the findings reported in this study may provide insight for designing effective and less toxic PAK4 inhibitors for triple negative breast cancer.

scholarly journals Molecular mechanism of anti-cancer activity of phycocyanin in triple-negative breast cancer cells

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Mathangi Ravi ◽  
Shilpa Tentu ◽  
Ganga Baskar ◽  
Surabhi Rohan Prasad ◽  
Swetha Raghavan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Molecular Mechanism ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Anti Cancer ◽  
Cancer Activity

scholarly journals Research on the Mechanism of Pulsatilla Potentially Useful for the Treatment of Triple Negative Breast Cancer Based on Network Pharmacology

2021 ◽  
Author(s):  
Shilin Li ◽  
Yi Fang
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Caspase 3 ◽  
Triple Negative ◽  
Age Of Onset ◽  
Network Pharmacology ◽  
Physical And Mental Health ◽  
Pulsatilla Chinensis ◽  
Potential Methods ◽  
Alternative Drugs

Abstract Triple negative breast cancer is a very malignant type of breast cancer. Its age of onset is young and the prognosis is poor, which seriously threatens women's physical and mental health. Pulsatilla Chinensis is a common medicine in traditional Chinese medicine. Application of network pharmacology analysis found that the active ingredients in Pulsatilla can target Caspase-3, NOS3, etc. to exert anti-tumor effects. This discovery will provide new alternative drugs and potential methods for the treatment of triple-negative breast cancer.

scholarly journals Molecular mechanism of gossypol mediating CCL2 and IL‑8 attenuation in triple‑negative breast cancer cells

2020 ◽  
Vol 22 (2) ◽  
pp. 1213-1226
Author(s):  
Samia Messeha ◽  
Najla Zarmouh ◽  
Patricia Mendonca ◽  
Carolyn Cotton ◽  
Karam Soliman
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Molecular Mechanism ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative

scholarly journals Maintaining oxidized H3 in heterochromatin is required for the oncogenic capacity of triple-negative breast cancer cells

2020 ◽  
Author(s):  
Gemma Serra-Bardenys ◽  
Tian Tian ◽  
Enrique Blanco ◽  
Jessica Querol ◽  
Laura Pascual-Reguant ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Histone Modification ◽  
Cancer Cells ◽  
Molecular Mechanism ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Essential Role ◽  
Triple Negative ◽  
Lysyl Oxidase ◽  
Histone H2a

SUMMARYThe histone modification of H3 oxidized at lysine 4 (H3K4ox) is catalyzed by lysyl oxidase–like 2 (LOXL2) and is enriched in heterochromatin in triple-negative breast cancer (TNBC) cells. Although H3K4ox has been linked to the maintenance of compacted chromatin, the molecular mechanism underlying this maintenance is unknown. Here we show that H3K4ox is read by the CRL4B complex, leading to the ubiquitination of histone H2A through the E3 ligase RBX1. Finally, interactions between RUVBL1/2 and LOXL2 are involved in the incorporation of the histone variant H2A.Z, which plays an essential role in the mechanism controlling the dynamics of oxidized H3. Maintenance of H3K4ox in chromatin is essential for heterochromatin properties, and disruption of any of the members involved in this pathway blocks the oncogenic properties of TNBC cells.

Molecular Mechanism by which Diosbulbin B Regulates the TP63 Gene in Triple-Negative Breast Cancer

2020 ◽  
Author(s):  
LIU LIU ◽  
Qiufeng Lao ◽  
Shengle Li ◽  
Weiyi Pang
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Molecular Mechanism ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
In Vitro Experiments ◽  
Active Components ◽  
Dioscorea Bulbifera

Abstract BackgroundDioscorea bulbifera L. is mainly used for antitumor therapy in clinical practice. Studies have shown that the drug-containing serum obtained from Dioscorea bulbifera L. induces the apoptosis and inhibits the proliferation of rat breast cancer cells. However, the main active compounds and the molecular mechanism in triple-negative breast cancer are still unclear.MethodsThe TCMSP, GeneCards, GEO and TCGA databases were used to identify genes that intersect the target genes of Dioscorea bulbifera L., active Dioscorea bulbifera L. components and triple-negative breast cancer targets, and Kaplan-Meier and GSEA methods were used to analyze the survival and pathway enrichment of the intersecting genes, respectively. Subsequently, in vitro experiments were performed for verification.ResultsA total of 14 active components were screened, and the targets of the active components were combined with triple-negative breast cancer-related targets and differentially expressed genes obtained from the GeneCards database. Three genes (CCNB1, PGR and TP63) are related to the anti-breast cancer effects of Dioscorea bulbifera L., and TP63 (P<0.05) is related to breast cancer survival. The GSEA showed that the TP63 gene is related to the apoptosis pathway, and TP63 gene analysis in the TCGA clinical database showed the greatest expression difference in triple-negative breast cancer. The in vitro experiments showed that diosbulbin B, the main antitumor compound in Dioscorea bulbifera L., may inhibit the proliferation and migration of MDA-MB-231 breast cancer cells and induce their apoptosis by promoting the expression of the TP63 gene.ConclusionThe present study fully elucidated the active components, potential targets and molecular mechanisms of Dioscorea bulbifera L. against triple-negative breast cancer and provided a new method for revealing the scientific basis and therapeutic mechanism of Chinese medicine in treating diseases.

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