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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
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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.
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Cisplatin is drug of choice toward cervical cancer despite having many side effects, thus researches are conducted in order to find the effective and synergistic co-chemoterapeutic agent combined with cisplatin. In this study, we observed the potential of the cinnamon essential oil (CEO) isolated from Cinnamomum burmannii as cochemoterapeutic agent of cisplatin on HeLa cells covering cytotoxic effect, cell cycle modulation and induction of apoptosis. Cytotoxic effect was determined by using MTT assay; while induction of apoptosis and cell cycle profile were observed by using flow cytometry. At 24 hours of incubation, CEO showed cytotoxic effect on HeLa cells with IC50 value of 250 μg/mL, while cisplatin showed cytotoxic effect with IC50 value of 18 μM. Combination of CEO and cisplatin reduced cells viability compared to cisplatin solely. Moreover, flow cytometry using annexin-V and PI showed that CEO and its combination with cisplatin induced apoptosis lower than cisplatin alone at 24 hours of incubation. Further analysis on the cell cycle progression showed that CEO induced S-phase arrest on HeLa cells, cisplatin induced G1 arrest, while combination of CEO and cisplatin induced G2/M arrest. Thus, the inhibition of HeLa cells growth at 24 hours is likely through cell cycle modulation rather than apoptosis.
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The selaginella ethanolic extract shows cytotoxic activity against T47D and MCF-7 cells. The aim of this research is to evaluate the cytotoxic effect and apoptosis induction of selaginella fractions on MCF-7 cells. The Selaginella plana powder was extracted by absolute ethanol. Ethanolic extract was dilluted by methanol:water (4:1) and then fractionated by hexane (S_Hex), methylene chloride (S_MTC), ethyl acetate (S_EA), and buthanol (S_BuOH). Cytotoxic activity was examined by MTT assay. Apoptosis examination used acrydine orangeetidium bromide staining (double staining). The result showed that the IC50 value of S_Hex, S_MTC, S_EA, and S_BuOH on MCF-7 cells were 30 μg/mL, 19 μg/mL, 24 μg/mL, and 2 μg/mL respectively. The active fractions (S_Hex, S_MTC, S_EA and S_BuOH) at its IC50 concentration increased apoptotic cells on the MCF-7 cells 35.33%, 20.33%, 24% and 45.67% respectively compared to control. Based on the result, buthanol fraction of Selaginella plana (S_BuOH) showed the highest apoptotic induction on MCF-7 cancer cells.
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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.
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Objective: To evaluate the effects of n-hexane insoluble fraction (HIF) of Ficus septica leaves in combination with doxorubicin on cytotoxicity, cell cycle and apoptosis induction of breast cancer T47D cell lines. Methods: The in vitro drugs-stimulated cytotoxic effects were determined using MTT assay. Analysis of cell cycle distribution was performed using flowcytometer and the data was analyzed using ModFit LT 3.0 program. Apoptosis assay was carried out by double staining method using ethydium bromide-acridin orange. The expression of cleaved-poly (ADP-ribose) polymerase (PARP) on T47D cell lines was identified using immunocytochemistry. Results:The combination exhibited higher inhibitory effect on cell growth than the single treatment of doxorubicin in T47D cells. In addition, combination of doxorubicin and HIF increased the incidence of cells undergoing apoptosis. HIF could improve doxorubicin cytotoxic effect by changing the accumulation of cell cycle phase from G2/M to G1 phase. The combination also exhibited upregulation of cleaved-PARP in T47D cells. Conclusions: Based on this results, HIF is potential to be developed as co-chemotherapeutic agent for breast cancer by inducing apoptosis and cell cycle arrest. However, the molecular mechanism need to be explored further.