AIM OF THE STUDY: To investigate the potential of F3 from S. crispus to prevent metastasis in breast cancer.
MATERIALS AND METHODS: The antimetastatic effects of F3 were first investigated on murine 4T1 and human MDA-MB-231 breast cancer cell (BCC) lines using cell proliferation, wound healing and invasion assays. A 4T1-induced mouse mammary carcinoma model was then used to determine the expression of metastasis tumor markers, epithelial (E)-cadherin, matrix metalloproteinase (MMP)-9, mucin (MUC)-1, nonepithelial (N)-cadherin, Twist, vascular endothelial growth factor (VEGF) and vimentin, using immunohistochemistry, following oral treatment with F3 for 30 days.
RESULTS: Significant growth arrest was observed with F3 IC50 values of 84.27 µg/ml (24 h) and 74.41 µg/ml (48 h) for MDA-MB-231, and 87.35 µg/ml (24 h) and 78.75 µg/ml (48 h) for 4T1 cells. F3 significantly inhibited migration of both BCC lines at 50 μg/ml for 24 h (p = 0.018 and p = 0.015, respectively). Similarly, significant inhibition of invasion was demonstrated in 4T1 (75 µg/ml, p = 0.016) and MDA-MB-231 (50 µg/ml, p = 0.040) cells compared to the untreated cultures. F3 treatment resulted in reduced tumor growth compared to untreated mice (p
AIM OF THE STUDY: To evaluate the immune stimulatory effects of F3 from S. crispus in NMU-induced rat mammary tumor model.
MATERIALS AND METHODS: Immunohistochemistry analysis of cellular immune parameters (CD4+ or CD8+ T cells, CIITA, MHC-II and CD68) was performed on NMU-induced rat mammary tumor nodules, followed by evaluation of the serum level of 34 cytokines using the cytokine antibody array.
RESULTS: Significant increase in MHC-II, CD4+ and CD8+ T cell and CIITA expression by tumor cells was observed in F3-treated rats compared to the tumor control group. F3-treated rats also displayed a significant decrease in the serum level of CCL2 and CD68+ infiltrating macrophages. Serum IFN-γ level in this group was increased by 1.7-fold suggesting enhanced infiltration of T cells, and upregulation of CIITA and MHC-II expression in the tumor cells might be triggered by F3-induced production of IFN-γ.
CONCLUSION: Our findings demonstrated for the first time that a subfraction from S. crispus, F3, is capable of activating the immune system in rats-bearing NMU-induced mammary tumor, which may contribute to the anticancer effects of F3, and additionally support the traditional use of S. crispus leaves to boost the immune system.
AIM OF THE STUDY: In this study, the effects of F3, lutein and β-sitosterol on tumor development and metastasis were investigated in 4T1-induced mouse mammary carcinoma model.
MATERIALS AND METHODS: Tumor-bearing mice were fed with F3 (100 mg/kg/day), lutein (50 mg/kg/day) and β-sitosterol (50 mg/kg/day) for 30 days (n = 5 each group). Tumor physical growth parameters, animal body weight and development of secondary tumors were investigated. The safety profile of F3 was assessed using hematological and histomorphological changes on the major organs in normal control mice (NM).
RESULTS: Our findings revealed significant reduction of physical tumor growth parameters in all tumor-bearing mice treated with F3 (TM-F3), lutein (TM-L) or β-sitosterol (TM-β) as compared with the untreated group (TM). Statistically significant reduction in body weight was observed in TM compared to the NM or treated (TM-F3, TM-L and TM-β) groups. Histomorphological examination of tissue sections from the F3-treated group showed normal features of the vital organs (i.e., liver, kidneys, lungs and spleen) which were similar to those of NM. Administration of F3 to NM mice (NM-F3) did not cause significant changes in full blood count values.
CONCLUSION: F3 significantly reduced the total tumor burden and prevented secondary tumor development in metastatic breast cancer without significant toxicities in 4T1-induced mouse mammary carcinoma model. The current study provides further support for therapeutic development of F3 with further pharmacokinetics studies.
DESIGN: Here, we have investigated these individual plant extracts and its synergistic mixture (PEM) for its anti-cariogenic effect to reduce populations of single and mixed-species of Streptococcus sanguinis and Streptococcus mutans in a planktonic or/and biofilm and their others reduced virulence. Bacterial populations in the biofilm after 24 h, hydrophobic cell surface activity to n-hexadecane and pH changes at 5 min' intervals until 90 min of incubation were recorded. Total phenolic content and bioactive compounds in the crude aqueous plant extracts were analysed. Regulatory gene expressions of S. mutans adhesins genes (gtfB, gtfC, gbpB and spaP) upon treatment with PEM were investigated in planktonic and biofilm conditions.
RESULTS: All plant extracts strongly reduced S. mutans in the biofilm compared to S. sanguinis in single and mixed-species. PEM reduced S. mutans by 84% with S. sanguinis 87% in the mixed population. Psidium sp. and PEM highly reduced cell-surface hydrophobicity of the two bacteria thus reducing adherence and biofilm formation. PEM and Mangifera sp. lowered initial pH change in the mixed populations of S. sanguinis and S. mutans. PEM downregulated the S. mutans gtfB gene expression in the single species planktonic and mixed-species biofilms.
CONCLUSIONS: The effectiveness of PEM in reducing S. mutans within the biofilm, cell-surface hydrophobicity, acid production and adhesin gene (gtfB) expression in mixed-species with S. sanguinis indicates its potential as an antibacterial agent against dental caries. This is attributed to the phenolic content in the PEM.
METHODS AND RESULTS: A total of 16 cannabinoids are determined in optimized microwave pretreatment of hemp oil using the developed approach. Untargeted metabolomics analysis reveals that cannabinoid extract (CE) and its major constituent (cannabidiol, CBD), can alleviate high glucose-induced increases in lipids and carbohydrates, and decreases in amino acid and nucleic acid. Moreover, CE and CBD are also found to suppress the expression levels of mdt-15, sbp-1, fat-5, fat-6, fat-7, daf-2, and elevate the expression level of daf-1, daf-7, daf-16, sod-3, gst-4, lipl-4, resulting in the decrease of lipid synthesis and the enhance of kinetism. Canonical correspondence analysis (CCA) uncovers strong associations between specific metabolic alterations and gene expression levels.
CONCLUSION: These findings from this exploratory study offer a new insight into the roles of cannabinoids in the treatment of obesity and related complications.
METHODOLOGY/PRINCIPAL FINDINGS: The hexane extract of C. cassia demonstrated high anti-proliferative activity against MCF-7 and MDA-MB-231 cells (IC50, 34 ± 3.52 and 32.42 ± 0.37 μg/ml, respectively). Oxidative stress due to disruption of antioxidant enzyme (SOD, GPx and CAT) activity is suggested as the probable cause for apoptosis initiation. Though the main apoptosis pathway in both cell lines was found to be through caspase-8 activation, caspase-9 was also activated in MDA-MB-231 cells but suppressed in MCF-7 cells. Gene expression studies revealed that AKT1, the caspase-9 suppressor, was up-regulated in MCF-7 cells while down-regulated in MDA-MB-231 cells. Although, AKT1 protein expression in both cell lines was down-regulated, a steady increase in MCF-7 cells was observed after a sharp decrease of suppression of AKT1. Trans-cinnamaldehyde and coumarin were isolated and identified and found to be mainly responsible for the observed anti-proliferative activity of CE (Cinnamomum cassia).
CONCLUSION: Activation of caspase-8 is reported for the first time to be involved as the main apoptosis pathway in breast cancer cell lines upon treatment with C. cassia. The double effects of C. cassia on AKT1 gene expression in MCF-7 cells is reported for the first time in this study.