ABSTRACT
Previously, berberine enhanced the sensitivity ofMichigan Cancer Foundation-7 (MCF-7)-resistant breast cancer cellstoward tamoxifen; however, its molecular mechanism remains unclear. The purpose of this study is to identify the potentialtargets and molecular mechanisms of berberine in overcoming breast cancer resistance toward tamoxifen by using abioinformatics approach for functional network analysis. The microarray data of tamoxifen-resistant and berberine-treatedMCF-7 cells were obtained from GSE67916 and GSE85871, which resulted in differentially expressed genes (DEGs).The analysis of the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment by using theDatabase for Annotation, Visualization, and Integrated Discovery revealed that several DEGs participated in the erbBtyrosine kinase signaling pathway. The analysis of protein–protein interaction network and hub gene selection by usingSTRING and Cytoscape identified the top 10 genes with the highest degree score. The analysis of genetic alterations byusing cBioPortal demonstrated the genetic alterations of six potential target genes, including protein kinase C alpha type(PRKCA), epidermal growth factor receptor (EGFR), erb-b2 receptor tyrosine kinase 4 (ERBB4), amphiregulin (AREG),estrogen receptor 1 (ESR1), and STAT1. Moreover, importantly, the erbB signaling is a potential target for overcomingbreast cancer resistance toward tamoxifen. Further studies are required to validate the results of this study
ABSTRACT
Long-term use of doxorubicin (DOX) causes several side effects, especially induction of metastasis, in breast cancercells. Pentagamaboronon-0 (PGB-0) or 2,5-bis(4-boronic acid benzylidene) cyclopentanone is a novel curcumin analogthat exerts cytotoxic effects on Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer cells. Theobjective of this study was to evaluate PGB-0 as a co-chemotherapeutic agent on DOX-induced metastatic breastcancer cells, 4T1. Potential cytotoxic and antimetastatic activities of PGB-0 were screened by molecular docking underPLANTS software, which revealed that the PGB-0 interacted with matrix metalloproteinase-9 (MMP-9) and InhibitorKappa β Kinase (IKKβ). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that PGB-0 andDOX exhibited cytotoxic effects on 4T1 breast cancer cells, with IC50 values of 294 and 2.4 µM, respectively, andsynergistically increased the cytotoxicity of DOX. Results of propidium iodide staining flow cytometry revealed thatthe PGB-0 and its combination with DOX induced cell cycle arrest in the S phase and the G2/M phase, respectively.In addition, PGB-0 and its combination with DOX induced apoptosis. Regarding the antimetastatic activity, a singletreatment with PGB-0 inhibited cell migration, while its combination with DOX inhibited cell migration with morepotency than that with single treatment, as assessed through wound healing assay. Gelatin zymography revealed thatthe PGB-0 and its combination with DOX inhibited MMP-9 activity. Immunoblotting assay showed that the PGB-0and its combination with DOX decreased the expression of Rac1 and p120. In conclusion, PGB-0 increased thecytotoxicity and inhibited the induction of metastasis by DOX in breast cancer cells.
ABSTRACT
Objective: To identify the potential target and mechanisms of hesperidin in MCF-7 estrogen receptor-positive breast cancer cells using bioinformatics approaches. Methods: Gene expression profiles were accessed from public database GSE85871. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was carried out with Database for Annotation, Visualization and Integrated Discovery. The protein-protein interaction network was analyzed by STRING-DB and visualized by Cytoscape. Transcription factor regulatory networks were constructed from TRED, TRRUST, RegNetwork and visualized by Cytoscape. Drug association analysis was conducted by WebGestalt. Results: GO and KEGG pathway enrichment analysis revealed biological processes, cellular components and molecular functions that were related to cancer and estrogen signaling pathways. KEGG pathway enrichment analysis of the genes in transcription factor-differential expression genes regulatory network showed regulation of cancer, estrogen signaling pathways, epidermal growth factor receptor tyrosine kinase inhibitor resistance, and endocrine resistance. Moreover, drug association analysis revealed that hesperidin affected the expression of the same gene as raloxifene. Conclusions: Hesperidin targets estrogen receptor signaling in estrogen receptor-positive breast cancer cells. Results of this study could trace the molecular mechanism of hesperidin in estrogen receptor-positive breast cancer cells and integrative bioinformatics analysis could accelerate drug discovery and development.
ABSTRACT
Objective:To observe the combination effect of doxorubicin andCitrus hystrix(kaffir lime’s) peel ethanolic extract(ChEE) on blood serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) activity and cardio-hepato-histopathology of femaleSpragueDawley rats. Methods:Doxorubicin andChEE(5 rats per group) were administered in five groups of3 rats each for11 d.GroupI: doxorubicin(dox)4.67 mg/kg body weight;GroupII: dox+ChEE500 mg/kg body weight;GroupIII: dox+ChEE1000 mg/kg body weight;GroupIV:ChEE1000 mg/kg body weight;GroupV: untreated(control).Results:ChEE repaired cardiohistopathology profile of doxorubicin induced cardiotoxicity and hepatotoxicity rats, but did not repair neither hepatohistopathology profile nor reduce serum activity ofALT andAST.Conclusion:ChEE has potency to be developed as cardioprotector agent in chemotherapy.