In the current study, the prognostic and predictive values of serum transforming growth factor-β1 (TGF-β1), insulin-like growth factor I (IGF-I)/IGF-I receptor (IGF-IR) and vascular endothelial growth factor-A (VEGF-A) were evaluated in triple-negative and non-triple-negative breast cancer (TNBC and non-TNBC). The aim was to identify a group of serological biomarkers and to identify possible candidates for targeted therapy in patients with TNBC and non-TNBC. Protein levels of TGF-β1, IGF-I/IGF-IR and VEGF-A in the serum were measured in 43 TNBC, 53 non-TNBC and 20 normal control participants using quantitative ELISA assays. Results were correlated against standard prognostic factors, response to treatment and survival. TNBC was identified to be associated with poor prognosis and serum levels of VEGF-A and IGF/IGF-IR were significantly higher in the TNBC group compared with the non-TNBC group. IGF-IR and VEGF-A overexpression was observed to be correlated with TGF-β1 expression and all of the markers investigated were associated with metastasis and disease progression. In the multivariate analysis, VEGF-A, IGF-I and IGF-IR were observed to be independent predictors for overall survival, whereas TGF-β1 and lymph node status were identified as independent predictors for disease-free survival. The overall response rate was significantly lower in patients with TNBC and those with high levels of TGF-β1, IGF-I/IGF-IR and VEGF-A. In view of the present results, it was concluded that TGF-β1, IGF-I/IGF-IR and VEGF-A overexpression is associated with the presence of aggressive tumors, which exhibit an increased probability of metastasis, a poor response to treatment and reduced survival rate. This indicates that VEGF-A, IGF-IR and IGF-I have the potential to be used as surrogate biomarkers and are promising candidates for targeted therapy, particularly in patients with TNBC.
Liver cancer is the fifth commonest malignancy worldwide and the third leading cause of death. Identifying novel curative and preventive therapy may improve its prognosis. In this study, thymoquinone (TQ), the most active biological ingredient of Nigella sativa Linn, was investigated for its antitumor activity. Mechanistic perspectives underlying this antitumor activity were explored by testing its effect on cell cycle, apoptosis, and angiogenesis. In addition, the chemopreventive effect of TQ was carried out by measuring its effect on phase I CYP1A1 and phase II glutathione S-transferase (GST) drug-metabolizing enzymes. The results of the present study revealed the effectiveness of TQ as an antitumor agent against different types of cancer including brain, colon, cervix and liver at both a time- and concentration-dependent manner. In HepG2 cells, it induced G2/M phase cell cycle arrest and a concentration-dependent increase in the percentage of apoptotic cells with an increase in the ratio of Bax/BCL-2. Moreover, the expression of mRNA and protein level of vascular endothelial growth factor decreased as the concentration of TQ increased. Our data showed a significant inhibition of induced phase I CYP1A1 enzyme, and elevation in the content of glutathione and activity of phase II enzyme GST, in HepG2 cells. Our results provide support for the beneficial use of TQ as a therapeutic and chemopreventive agent against liver cancer.
Metabolic profiling of the hexane extract and essential oil of Cordia africana Lam., an 9 economically important agroforestry species, was analysed by GC-FID and GC-MS. 10Cytotoxicity was assessed in MCF-7 cancer cells using sulphorhodamine-B assay. 11Caspase-8, BcL-2 and Ki-67 levels were evaluated using enzyme-linked 12 immunosorbent assay. Forty-one compounds were identified in the hexane extract, 13 meanwhile, eighty compounds were annotated in the essential oil. n-Decane (9.52%), 14 -sitosterol (8.13%), undecane (6.32%) and palmitaldehyde (5.50 %) were the major 15 compounds identified in the hexane extract, whereas, -caryophyllene (32.0%), 16 germacrene D (10.12%) and δ-cadinene (7.20%) predominated in the essential oil. The 17 inhibitory concentrations (IC 50 ) of the extract and oil were 4.55 µg/mL and 12.90 18 µg/mL, respectively. Caspase-8 activity increased significantly in hexane extract 19 treated cells. Furthermore, BcL-2 and Ki-67 protein expression levels were 20 significantly decreased. Cordia africana Lam exhibits potent cytotoxicity against breast 21 cancer cell line, most likely through apoptosis regulation.
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