METHODS: EEP was obtained by maceration with absolute ethanol, then it was concentrated in rotaevaporator up to complete evaporation of the solvent. The crude extract was fractionated with hexane, ethyl acetate, chloroform and methanol and they were subjected to phytochemical screening and total phenolic compounds. Antioxidant activity of EEP and fractions was done by means of the 2,2-diphenyl-1-picryhydrazyl (DPPH) method. Biomarkers of red propolis were identified by LC-Orbitrap-FTMS. To assess cytotoxic activity of the extract, cells were exposed to EEP over 72 h. Cell viability was assessed by means of MTT assay. The percentage of cell growth inhibition (IC50) was analysed by means of non-linear regression, and the absorbance values of the various investigated concentrations were subjected to one-factor analysis of variance (ANOVA) followed by Tukey's or Tamhane's tests (α = 0.05).
RESULTS: The results obtained using phytochemical screening and LC-Orbitrap-FTMS indicated the presence of phlobaphene tannins, catechins, chalcones, aurones, flavonones, flavonols, xanthones, pentacyclic triterpenoids and guttiferones in Brazilian red propolis. EEP and its hexane, chloroform and ethyl acetate fractions obtained by liquid-liquid partitioning exhibited satisfactory antioxidant percentages. EEP (IC50 cell lines tested when compared to negative control.
CONCLUSIONS: C-Orbitrap-FTMS was useful to establish the chemical profile of the red propolis. Brazilian red propolis has antioxidant properties and decreases substantially the percentage of cell survival of human tumour cells; thus, it has potential to serve as an anticancer drug.
METHODS: Characterization of the synthesized AuNPs was done by different techniques such as ultraviolet-visible spectrum absorption, X-ray diffraction, dynamic light scattering, Fourier transform infrared spectroscopy, transmission electron microscopy, and energy-dispersive X-ray analysis.
RESULTS: All the results showed the successful green synthesis of AuNPs from Sx, which induced apoptosis of C666-1 cell line (NPC cell line). There was a decline in both cell viability and colony formation in C666-1 cells upon treatment with Sx-AuNPs. The cell death was proved to be caused by autophagy and mitochondrial-dependent apoptotic pathway.
CONCLUSION: Thus, due to their anticancer potential, these nanoparticles coupled with Sx can be used for in vivo applications and clinical research in future.
MATERIALS AND METHODS: Five groups of rats (n=6) were administered orally once daily for 7 days with 8% Tween 80 (negative control), 100 mg/kg ranitidine (positive control), or MEMC (100, 250 or 500 mg/kg), followed by the ulcer induction via ligation of the pyloric part of the rat's stomach. This was followed by the macroscopic analysis of the stomach, evaluation of gastric content parameters, and quantification of mucus content. The antioxidant (measured using the superoxide anion and 2,2-diphenyl-1-picrylhydrazyl (DPPH)-radical scavenging, oxygen radical absorbance capacity (ORAC) and total phenolic content (TPC) assays), anti-inflammatory (evaluated using the in vitro lipoxygenase and xanthine oxidase assays), phytoconstituents and HPLC analysis of MEMC were also carried out.
RESULTS: The MEMC significantly (p<0.05) reduced gastric lesion in this model. Furthermore, the extract also significantly (p<0.01) reduced the volume of gastric content whereas the total acidity was significantly (p<0.05) reduced in the doses of 100 and 500 mg/kg MEMC. Moreover, the mucus content increased significantly (p<0.01) in MEMC-treated rats. The extract also showed high antioxidant and anti-inflammatory activities in all assays tested, and demonstrated the presence of high tannins and saponins followed by flavonoids.
CONCLUSION: The MEMC exerted gastroprotective effect via several mechanisms including the anti-secretory, antioxidant and anti-inflammatory activities. These activities could be attributed to the presence of tannins, saponins and flavonoids (e.g. rutin, quercitrin, fisetin and dihydroquercetin).
Purpose: To study EGFR alterations and expressions in a multi ethnic Malaysian TNBC patient cohort to determine the possibility of using anti-EGFR combinatorial therapy for this population.
Patients and methods: In this study, we evaluated 58 cases of Malaysian TNBC patient samples for EGFR gene copy number alteration and EGFR protein overexpression using fluorescence in-situ hybridization (FISH) and immunohistochemistry (IHC) methods, respectively.
Results: EGFR protein overexpression was observed in about 30% while 15.5% displayed high EGFR copy number including 5.17% gene amplification and over 10% high polysomy. There is a positive correlation between EGFR protein overexpression and gene copy number and over expression of EGFR is observed in ten out of the 48 low copy number cases (20.9%) without gene amplification.
Conclusion: This study provides the first glimpse of EGFR alterations and expressions in a multi ethnic Malaysian TNBC patient cohort emphasising the need for the nationwide large scale EGFR expression evaluation in Malaysia.
Objective: In this study, bystander effects in MCF-7 breast cancer cells and hFOB 1.19 normal osteoblast cells irradiated with gamma emitting HDR Brachytherapy Ir-192 source were investigated.
Material and Methods: In this in-vitro study, bystander effect stimulation was conducted using medium transfer technique of irradiated cells to the non-irradiated bystander cells. Cell viability, reactive oxygen species (ROS) generation and colony forming assay was employed to evaluate the effect.
Results: Results indicate that the exposure to the medium irradiated MCF-7 induced significant bystander killing and decreased the survival fraction of bystander MCF-7 and hFOB from 1.19 to 81.70 % and 65.44 %, respectively. A significant decrease in survival fraction was observed for hFOB 1.19 bystander cells (p < 0.05). We found that the rate of hFOB 1.19 cell growth significantly decreases to 85.5% when added with media from irradiated cells. The ROS levels of bystander cells for both cell lines were observed to have an increase even after 4 h of treatment. Our results suggest the presence of bystander effects in unirradiated cells exposed to the irradiated medium.
Conclusion: These data provide evidence that irradiated MCF-7 breast cancer cells can induce bystander death in unirradiated MCF-7 and hFOB 1.19 bystander cells. Increase in cell death could also be mediated by the ROS generation during the irradiation with HDR brachytherapy.
PURPOSE: Here, we investigated whether OSCC cells were sensitive towards zerumbone treatment and further determined the molecular pathways involved in the mechanism of action.
METHODS: Cytotoxicity, anti-proliferative, anti-migratory and anti-invasive effects of zerumbone were tested on a panel of OSCC cell lines. The mechanism of action of zerumbone was investigated by analysing the effects on the CXCR4-RhoA and PI3K-mTOR pathways by western blotting.
RESULTS: Our panel of OSCC cells was broadly sensitive towards zerumbone with IC50 values of less than 5 µM whereas normal keratinocyte cells were less responsive with IC50 values of more than 25 µM. Representative OSCC cells revealed that zerumbone inhibited OSCC proliferation and induced cell cycle arrest and apoptosis. In addition, zerumbone treatment inhibited migration and invasion of OSCC cells, with concurrent suppression of endogenous CXCR4 protein expression in a time and dose-dependent manner. RhoA-pull down assay showed reduction in the expression of RhoA-GTP, suggesting the inactivation of RhoA by zerumbone. In association with this, zerumbone also inhibited the PI3K-mTOR pathway through the inactivation of Akt and S6 proteins.
CONCLUSION: We provide evidence that zerumbone could inhibit the activation of CXCR4-RhoA and PI3K-mTOR signaling pathways leading to the reduced cell viability of OSCC cells. Our results suggest that zerumbone is a promising phytoagent for development of new therapeutics for OSCC treatment.
METHODS: The phytochemical and biological criteria of A. zerumbet were in vitro investigated as well as in mouse xenograft model.
RESULTS: A. zerumbet extracts, specially CH2Cl2 and MeOH extracts, exhibited the highest potent anti-tumor activity against Ehrlich ascites carcinoma (EAC) cells. The most active CH2Cl2 extract was subjected to bioassay-guided fractionation leading to isolatation of the naturally occurring 5,6-dehydrokawain (DK) which was characterized by IR, MS, 1H-NMR and 13C-NMR. A. zerumbet extracts, specially MeOH and CH2Cl2 extracts, exhibited significant inhibitory activity towards tumor volume (TV). Furthermore, A. zerumbet extracts declined the high level of malonaldehyde (MDA) as well as elevated the levels of superoxide dismutase (SOD) and catalase (CAT) in liver tissue homogenate. Moreover, DK showed anti-proliferative action on different human cancer cell lines. The recorded IC50 values against breast carcinoma (MCF-7), liver carcinoma (Hep-G2) and larynx carcinoma cells (HEP-2) were 3.08, 6.8, and 8.7 µg/mL, respectively.
CONCLUSION: Taken together, these findings open the door for further investigations in order to explore the potential medicinal properties of A. zerumbet.