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.

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.

OBJECTIVETo 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.

METHODSThe 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.

RESULTSThe 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.

CONCLUSIONSBased 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.

Antineoplastic Agents ; chemistry ; pharmacology ; Apoptosis ; drug effects ; Breast Neoplasms ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; Doxorubicin ; pharmacology ; Female ; Ficus ; chemistry ; Flow Cytometry ; Hexanes ; chemistry ; pharmacology ; Humans ; Immunohistochemistry ; Solubility

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.

OBJECTIVETo observe the combination effect of doxorubicin and Citrus hystrix (kaffir lime's) peel ethanolic extract (ChEE) on blood serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity and cardio-hepato-histopathology of female Sprague Dawley rats.

METHODSDoxorubicin and ChEE (5 rats per group) were administered in five groups of 3 rats each for 11 d. Group I: doxorubicin (dox) 4.67 mg/kg body weight; Group II: dox+ChEE 500 mg/kg body weight; Group III: dox+ChEE 1 000 mg/kg body weight; Group IV: ChEE 1 000 mg/kg body weight; Group V: untreated (control).

RESULTSChEE repaired cardiohistopathology profile of doxorubicin induced cardiotoxicity and hepatotoxicity rats, but did not repair neither hepatohistopathology profile nor reduce serum activity of ALT and AST.

CONCLUSIONChEE has potency to be developed as cardioprotector agent in chemotherapy.

Alanine Transaminase ; blood ; metabolism ; Animals ; Aspartate Aminotransferases ; blood ; metabolism ; Citrus ; chemistry ; Doxorubicin ; pharmacology ; toxicity ; Female ; Heart ; drug effects ; Liver ; drug effects ; metabolism ; pathology ; Myocardium ; metabolism ; pathology ; Plant Extracts ; chemistry ; pharmacology ; Protective Agents ; chemistry ; pharmacology ; Rats