RESUMEN
Flavonoids have a pivotal cytotoxic effect against hepatocellular carcinoma (HCC). The current study aimed to investigate which flavonoid isolated from Physalis pubescens L. leaves has the most cytotoxic effect against Hep-G2 liver cancer cells and if it could ameliorate epirubicin efficacy and safety. Baicalein trimethyl ether (BTME), rutin, quercitrin and myricitrin were isolated from Physalis Pubescens L. leaves. Hep-G2 cells were treated with the isolated flavonoids as well as a combination of BTME and epirubicin. Cell viability and the chromosomal DNA fragmentation in Hep-G2 cells were assessed. BTME showed the best cytotoxic effect against Hep-G2 cells. Combination of epirubicin with (200 µg/mL) BTME significantly decreased the IC50 of epirubicin from 2.79 ± 0.626 µg/mL to 0.76 ± 0.258 µg/mL. Moreover, the same combination significantly increased the IC50 of BTME against WI-38 normal cells. DNA fragmentation as well as the concentration of beclin 1 and Bax were significantly increased in Hep-G2 cells treated with BTME and BTME+epirubicin compared to untreated cells. Besides, BTME and BTME+epirubicin significantly decreased the gene expression of TGFß1 whereas increased ATG-7 gene expression. Conclusions: BTME (200µg/mL) significantly enhanced epirubicin's cytotoxicity against Hep-G2 cells and ameliorated its safety profile. BTME could exert anti-hepatocarcinoma effect by enhancing apoptosis and autophagy.
Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Flavanonas , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Epirrubicina , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Apoptosis , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Células Hep G2 , Flavonoides/farmacología , AutofagiaRESUMEN
OBJECTIVES: Grape seed oil (GSO) has recently gained popularity due to its anticancer properties. This study aimed to investigate the efficacy of combining cisplatin (CP) and GSO in tongue squamous cell carcinoma (TSCC) treatment. METHODS: In this study, human tongue carcinoma cell line (HNO-97) was treated with CP and GSO alone or in combination. The effects of CP and GSO on cytotoxicity and cell cycle arrest were studied using the MTT assay and flowcytometry, respectively. The apoptotic markers, including p53 and caspase 8, were assessed using reverse-transcription polymerase chain reaction (RT-PCR), caspase 3 using immunohistochemistry, and the angiogenic marker vascular endothelial growth factor (VEGF) using enzyme-linked immunosorbent assay (ELISA). RESULTS: The IC50 drug concentrations were found to be 16.4 ug/mL of GSO and 2.18 ug/mL of CP. When compared to the untreated control group, the percentage of S phase cells and apoptotic cells was significantly higher in the GSO, CP, and GSO/CP combination therapy groups. Furthermore, p53, caspase 8, caspase 3 expression were significantly upregulated in the GSO-and CP-treated groups, with evident upregulation with GSO/CP combination therapy. However, VEGF levels were significantly lower in the GSO-, CP-, and combined GSO/CP-treated groups. CONCLUSIONS: GSO has both an apoptotic and antiangiogenic effect in the treatment of TSCC, suggesting a new strategy for phytochemical-based combination therapy.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de la Lengua , Vitis , Humanos , Cisplatino/farmacología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Caspasa 3/metabolismo , Caspasa 8 , Vitis/metabolismo , Proteína p53 Supresora de Tumor , Apoptosis , Neoplasias de la Lengua/tratamiento farmacológico , Neoplasias de la Lengua/patología , Adyuvantes Inmunológicos/farmacología , Aceites de Plantas/farmacología , Lengua/patología , Línea Celular Tumoral , Proliferación CelularRESUMEN
X-ray repair cross-complementing group 1 (XRCC1), a coordinator protein of the DNA repair complex, is thought to be involved in cancer progression. This case-control study aimed to investigate the association of two biallelic single-nucleotide polymorphisms (SNPs; Arg399Gln, Arg194Trp) of the XRCC1 gene with its tissue expression level and breast cancer (BC) risk in Egyptian women. This study included 100 BC female patients (case group 1) and 100 healthy females (control group 2). The XRCC1 tissue expression was assessed by immunohistochemistry (IHC). Genotyping of the two XRCC1 SNPs (Arg399Gln, Arg194Trp) using real-time polymerase chain reaction (PCR) was also conducted. The XRCC1 expression level was significantly lower in cancerous tissues than adjacent non-cancerous tissues (p < .001). The XRCC1 399Gln/Gln genotype, 399Gln allele, the dominant, and recessive models were significantly associated with lower XRCC1 expression in breast cancerous tissues and increased risk for BC (3.390-, 1.965-, 2.241-, and 2.429-folds, respectively). The XRCC1 399Gln/Gln genotype was associated with lower incidence of advanced tumor grade (OR: 0.06; 95%CI: 0.01-0.74; p = .028). Conversely, the XRCC1 Arg194Trp polymorphism did not show any significant association with either XRCC1 expression in breast cancer tissues or BC risk in all genetic models. The XRCC1 haplotypes, 399Gln/194Arg and 399Gln/194Trp, were associated with 1.800- and 1.675-folds risk for BC, respectively. The XRCC1 gene polymorphism (Arg399Gln) is associated with reduced XRCC1 tissue expression and enhanced BC risk with a well-differentiated nature in Egyptian women. Moreover, XRCC1 haplotypes, 399Gln/194Arg and 399Gln/194Trp, were associated with increased BC risk.