RESUMEN
The current study was designed to unveil the anticancer effects of naringenin against breast cancer MDA-MB-231 cells. Cytotoxic effects were estimated via MTT viability assay. Clonogenic assay was performed to assess clonogenic potential of MDA-MB-231 cells. Apoptosis was examined via AO/EB staining, quantified via annexin V/PI staining and western blotting was performed to monitor apoptosis allied protein expressions. Cell cycle was analyzed through flow cytometric analysis. Transwell chambers assay was executed for determination of cell migration and cell invasion tendency of MDA-MB-231 breast cancer cells. Results indicated significant anticancer potential of naringenin drug against MDA-MB-231 cells. On evaluation of cell proliferation rate of breast cancer cells by MTT assay, it was observed that naringenin inhibited proliferation rate in dose as well as time dependent manner. AO/EB staining assay revealed potential morphological changes indicating apoptotic cell death. Annexin V/PI staining assay revealed increased apoptotic cell percentage with increased drug doses. The apoptosis inducing potential of naringenin drug was observed to be mediated via caspase activation. Flow cytometric analysis predicted cell cycle arrest at G2/M phase of cell cycle. Further cell migration as well as cell invasion tendency of MDA-MB-231 cells was reduced to minimum upon application of naringenin drug.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Caspasas/metabolismo , Flavanonas/farmacología , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Antineoplásicos Fitogénicos/química , Western Blotting , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Flavanonas/química , Humanos , Estructura Molecular , Metástasis de la Neoplasia , Factores de TiempoRESUMEN
BACKGROUND: We previously showed that human papillomavirus (HPV) serostatus was not an independent risk factor for esophageal squamous cell carcinoma(ESCC) in nonsmokers and nondrinkers; however, HPV increased the risk in smokers. METHODS: Here we investigated possible interactions between HPV16 serostatus and three susceptibility loci identified in GWASs at apoptosis associated genes with regard to risk of ESCC in a case-control study of 313 patients with ESCC and 314 healthy controls. The loci (CHK2 rs738722, C12orf51 rs2074356, and PLCE1 rs2274223) were genotyped, and the presence or absence of HPV16 in serum was measured by ELISA. Multivariable logistic regression was used to evaluate possible interactions of HPV16 serostatus and the three loci on the risk of ESCC. RESULTS: A significant interaction was found between HPV16 serology and rs2074356 (P = 0.005, odds ratio [OR] 1.40, 95% confidence interval [CI] 1.11-1.77) or rs2274223 (P < 0.001, OR 1.53, 95% CI 1.23-1.91), but not for rs738722. For rs2074356, risk of ESCC was increased substantially in smokers (P < 0.001, OR 8.25, 95% CI 3.84-17.71) and drinkers (OR4.04, P = 0.001, 95% CI 1.79-9.10) who carried risk alleles (TT or TC genotype) and were HPV16-seropositive. Similar results were observed for rs2274223 in smokers (P < 0.001, OR6.06, 95% CI 2.85-12.88) and drinkers (P < 0.001, OR 5.43, 95% CI 2.51-11.76), but not for rs738722. CONCLUSION: Consistent with the previous study, loci at rs2074356 and rs2274223 could increase the risk of ESCC, furthermore, there were significant interactions between HPV sero-status and the susceptibility loci on the risk of ESCC. This effect could be modified obviously by smoking and drinking.
Asunto(s)
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/virología , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/virología , Papillomavirus Humano 16/inmunología , Fosfoinositido Fosfolipasa C/genética , Ubiquitina-Proteína Ligasas/genética , Anciano , Consumo de Bebidas Alcohólicas/genética , Apoptosis , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/diagnóstico , Carcinoma de Células Escamosas de Esófago , Femenino , Sitios Genéticos , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/inmunología , Infecciones por Papillomavirus/virología , Polimorfismo de Nucleótido Simple , Fumar/genéticaRESUMEN
Circular RNAs (circRNAs) are associated with the progression of gastric cancer (GC). This study investigates the regulation of the circular RNA, hsa_circ_0119412 in GC and its effects on GC cells. The expression of hsa_circ_0119412, microRNA (miR)-1298-5p, and zinc finger BED-type containing 3 (ZBED3) were measured by quantitative reverse transcription-PCR (qRT-PCR) and Western blotting. The cell counting kit-8 (CCK-8) assay, flow cytometry, transwell, and animal assays were performed to identify the roles of hsa_circ_0119412, miR-1298-5p, and ZBED3 in the viability, apoptosis, invasion, and growth of GC cells. The relationship between hsa_circ_0119412, miR-1298-5p, and ZBED3 was confirmed by luciferase, RNA immunoprecipitation (RIP), and RNA pull-down assays. Our data revealed that hsa_circ_0119412 and ZBED3 expression was upregulated in GC, while miR-1298-5p expression was downregulated. Both the knockdown of hsa_circ_0119412/ZBED3 and miR-1298-5p overexpression inhibited GC cell growth and invasion, and enhanced cell apoptosis, while miR-1298-5p interference or ZBED3 overexpression showed the opposite trend. Mechanistically, hsa_circ_0119412 sponges miR-1298-5p, which regulates ZBED3 expression. Silencing hsa_circ_0119412 inhibits the progression of GC, at least in part, by targeting the miR-1298-5p/ZBED3 axis.