scholarly journals Combination of 5-fluorouracil and Lipopolysaccharide Synergistically Induces Cytotoxicity and Apoptosis in MCF-7 Human Breast Cancer Cells

Author(s):  
Negin Nokhandani ◽  
Mahdieh Naghavi Alhosseini ◽  
Ali Memarian ◽  
Homa Davoodi

Several studies have been conducted to find suitable combinations of drugs to increase the efficacy of chemotherapy and reduce the resistance of tumor cells to treatment. Lipopolysaccharide (LPS), as a ligand for Toll-like receptor 4 (TLR-4), can modify immune responses in different cancers. Although multiple studies have been performed in this area, the effect of LPS on tumor cells remains controversial. In the present study, the cytotoxic effects of 5-fluorouracil (5-FU), with or without LPS, were evaluated in human breast cancer cell line (MCF-7) on apoptosis and gene expression in downstream signaling pathways. MCF-7 was obtained from the Pasteur Institute of Iran. The effects of LPS and 5-FU on cytotoxicity, apoptosis, and gene expression in NF-κB, ERK, and AKT signaling pathways were evaluated by MTT assay, Annexin V/propidium iodide (PI) apoptosis assay, and qRTPCR, respectively. Our findings showed that LPS alone did not significantly affect cytotoxicity or apoptosis, compared to the control cells (untreated cells), while combined with 5-FU, it caused a significant increase in the apoptosis of cancer cells and decreased cell viability. It was also concluded that LPS in combination with 5-FU increased TLR-4 expression and downregulated gene expression in NF-κB, ERK, and AKT pathways (p=0.001). Although the role of LPS in tumor inhibition or progression remains controversial, our findings suggest that LPS can be considered a novel complementary approach intranslational oncology research of breast cancer therapy.

Author(s):  
Carolina Alonso-Gonz�lez ◽  
Javier Men�ndez-Men�ndez ◽  
Alicia Gonz�lez-Gonz�lez ◽  
Alicia Gonz�lez ◽  
Samuel Cos ◽  
...  

2002 ◽  
Vol 29 (3) ◽  
pp. 305-317 ◽  
Author(s):  
C Vyhlidal ◽  
X Li ◽  
S Safe

Transferrin (Tf) is an iron transport protein expressed in MCF-7 human breast cancer cells. In nuclear run-on assays, 17beta-estradiol (E2) increased the rate of Tf gene expression approximately 3-fold within 1 h after treatment and reporter gene activity was also induced in MCF-7 cells transfected with a construct containing a -3600 to +39 Tf gene promoter insert. Deletion and mutation analysis identified an E2-responsive promoter region between -811 and -762, which was GC-rich (80%) and contained two nonconsensus estrogen response elements (EREs). E2-responsiveness of this region was associated with a GGACA(N)(3)TGGCC motif (-803 to -791) which bound human estrogen receptor alpha (hERalpha) in gel mobility shift assays. In Drosophila Schneider SL-2 cells, the -811 to -752 was E2-responsive after cotransfection with hERalpha expression plasmid plus E2, whereas Sp1 protein did not induce transactivation. These studies confirm that E2 induces Tf gene expression through a nonconsensus distal ERE.


2021 ◽  
Author(s):  
P.Suganya devi ◽  
M.Saravana kumar ◽  
S.Mohan das

Abstract Aims: The aim of our research was to isolate anthocyanin from red sorghum bran and to study its effects on p53 and bcl 2 gene expressions in Human Breast cancer cell line (MCF-7). Main methods: Two compounds were isolated from red sorghum bran by using Sephadex LH-20 column chromatography. The antiproliferative activity of isolated compounds were analysed by MTT assay and the expression studies were performed by RT-PCR analysis.Key findings: Our research focusing on apigenin-5-β-D-glucopyranoside and luteolin-5-β-D-glucopyranoside another compound as a potention anticancer agent have demonstrated that the compounds isolated from red sorghum bran inhibited breast cancer cell lines by up regulation of P53 gene expression and down regulation of Bcl 2 gene expression. Significance: In conclusion, the two compounds isolated from red sorghum bran, were effective in up regulation of P53 and down regulation of Bcl 2 gene expression.


2018 ◽  
Vol 70 (4) ◽  
pp. 639-645 ◽  
Author(s):  
Hossein Abbaspour ◽  
Afshar Safipour

Curcumin is the active ingredient of Curcuma longa, which inhibits the development of malignant cells. Prevention and treatment of cancer by natural compounds, especially curcumin, and understanding the mechanism of action, is an area of interest in cancer research. In this study, we evaluated the effects of curcumin on cell proliferation, ornithine decarboxylase 1 (ODC1) and adenosine deaminase (ADA) gene expression in human breast cancer cell line (MCF-7) as compared to the non-cancer line (MCF-10A). Both cell lines were subjected to increasing doses of curcumin, ranging from 0 to 30 ?g/mL. Cell viability was quantified by the MTT assay. In vitro clonogenic survival assay was performed on MCF-7 cells. Expression of ADA and ODC1 were analyzed by Western blotting and qRT-PCR. Curcumin inhibited the growth of malignant cells in a time- and dose-dependent manner. The calculated IC50 value for MCF-7 cells in 48 h was 12 ?g/mL. Forty-five to 70% decreases in colony formation were observed in MCF-7 cells treated with 30-60 ?g/mL curcumin, respectively. Our data revealed a dose-dependent downregulation of ODC1 and ADA expression and respective enzyme activities by curcumin, which correlated with decreased proliferation in the MCF-7 breast cancer cell line. These data suggest that curcumin represses the proliferation of breast cancer cells through downregulation of ODC1 and ADA gene expression, which might be another mechanism of curcumin-mediated tumor growth inhibition.


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