Combined treatment of menadione and calcitriol increases the antiproliferative effect by promoting oxidative/nitrosative stress, mitochondrial dysfunction, and autophagy in breast cancer MCF-7 cells

2020 ◽  
Vol 98 (8) ◽  
pp. 548-556
Author(s):  
Solange Guizzardi ◽  
Gabriela Picotto ◽  
Valeria Rodriguez ◽  
JoEllen Welsh ◽  
Carmen Narvaez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Nitrosative Stress ◽  
Combined Therapy ◽  
Combined Treatment ◽  
Single Agent ◽  
Coupling Efficiency ◽  
Antiproliferative Action ◽  
Oncogenic Pathways ◽  
Mcf 7

The aim of this study was to determine new insights into the molecular mechanisms involved in the antiproliferative action of menadione + calcitriol (MEN+D) on MCF-7 cells. After 24 h, MEN+D inhibited the cell growth but was not observed with each single treatment. The combined drugs reduced the mitochondrial respiration at that time, as judged by an increase in the proton leak and a decrease in the ATP generation and coupling efficiency. At longer times, 48 or 96 h, either D or MEN reduced the proliferation, but the effect was higher when both drugs were used together. The combined treatment increased the superoxide anion ([Formula: see text]) and nitric oxide (NO•) contents as well as acidic vesicular organelles (AVOs) formation. The percentage of cells showing the lower mitochondrial membrane potential (ΔΨm) was highly increased by the combined therapy. LC3-II protein expression was enhanced by any treatment. In conclusion, the antiproliferative action of MEN+D involves oxidative/nitrosative stress, mitochondrial alteration, and autophagy. This combined therapy could be useful to treat breast cancer cells because it inhibits multiple oncogenic pathways more effectively than each single agent.

scholarly journals The Effect of Canertinib on Sensitivity of Cytotoxic Drugs in Tamoxifen-Resistant Breast Cancer Cells In Vitro

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Hesham A. M. Gomaa ◽  
Asmaa T. Ali ◽  
M. Abdel Gabbar ◽  
M. A. Kandeil
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Kinase Inhibitor ◽  
Apoptotic Cell ◽  
Combined Treatment ◽  
Single Agent ◽  
Tamoxifen Resistance ◽  
Cytotoxic Drugs ◽  
Mcf 7

Aims and Objectives. To investigate and examine the reversal effects of canertinib on the activity of EGFR and tamoxifen resistance in drug-resistant human breast carcinoma cells (MCF-7/TamR). Materials and Methods. The antiproliferative activity of canertinib alone or in combination with a conventional EGFR-targeting chemotherapies cytotoxic drugs differing in the mechanism(s) of action, such as paclitaxel, carboplatin, etoposide, vinorelbine, and daunorubicin as well as resistance mechanisms of EGFR targeting, have been investigated. Results. With an elevated dosage of canertinib, a significant decrease in proliferation and increase in apoptosis was observed. The treatment with higher doses of canertinib resulted in a 2-3-fold increase in apoptosis. In the combined treatment, it had been noticed a significant developed apoptotic cell death rather induced by single agent treatment. A significant downregulation of the antiapoptotic protein bcl-2 was exposed by immunocytochemistry investigation. Sensitivity to paclitaxel was also measured and was found to inversely correlate to bcl-2 status. Conclusion. Proliferation inhibition and apoptosis in MCF-7/TAM-R cells increase with increasing dosage of canertinib. This suggests that canertinib can reverse tamoxifen resistance in breast cancer cells. The antitumor effect of this EGFR-irreversible tyrosine kinase inhibitor provides a rationale for its clinical evaluation in combination with other cytotoxic drugs.

Molecular Mechanisms Underlying the Anti-Breast Cancer Stem Cell Activity of Pterocladia capillacea and Corallina officinalis Polysaccharides

2021 ◽  
Vol 21 ◽  
Author(s):  
Hebatallah G. Hafez ◽  
Rafat M. Mohareb ◽  
Sohair M. Salem ◽  
Azza A. Matloub ◽  
Emad F. Eskander ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Protein Complexes ◽  
Cell Activity ◽  
Sulfated Polysaccharide ◽  
Corallina Officinalis ◽  
Stem Cell Activity ◽  
Mcf 7

Objective: This study aimed to appraise the activity of Pterocladia capillacea and Corallina officinalis polysaccharides against breast cancer stem cells (BCSCs). P. capillacea and C. officinalis polysaccharides were characterized to be sulfated polysaccharide-protein complexes. Methods: Cytotoxicity of the polysaccharides against MDA-MB-231 and MCF-7 cell lines along with their impact on CD44+/CD24− and aldehyde dehydrogenase 1(ALDH1) positive BCSC population were determined. Their effect on gene expression of CSC markers, Wnt/β-catenin and Notch signaling pathways was evaluated. Results: P. capillacea and C. officinalis polysaccharides inhibited the growth of breast cancer cells and reduced BCSC subpopulation. P. capillacea polysaccharides significantly down-regulated OCT4, SOX2, ALDH1A3 and vimentin in MDA-MB-231 as well as in MCF-7 cells except for vimentin that was up-regulated in MCF-7 cells. C. officinalis polysaccharides exhibited similar effects except for OCT4 that was up-regulated in MDA-MB-231 cells. Significant suppression of Cyclin D1 gene expression was noted in MDA-MB-231 and MCF-7 cells treated with P. capillacea or C. officinalis polysaccharides. β-catenin and c-Myc genes were significantly down-regulated in MDA-MB-231 cells treated with C. officinalis and P. capillacea polysaccharides, respectively, while being up-regulated in MCF-7 cells treated with either of them. Additionally, P. capillacea and C. officinalis polysaccharides significantly down-regulated Hes1 gene in MCF-7 cells despite increasing Notch1 gene expression level. However, significant down-regulation of Notch1 gene was observed in MDA-MB-231 cells treated with P. capillacea polysaccharides. Conclusion: Collectively, this study provides evidence for the effectiveness of P. capillacea and C. officinalis polysaccharides in targeting BCSCs through interfering with substantial signaling pathways contributing to their functionality.

scholarly journals Dasatinib Treatment Increases Sensitivity to c-Met Inhibition in Triple-Negative Breast Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 548 ◽  
Author(s):  
Patricia Gaule ◽  
Nupur Mukherjee ◽  
Brendan Corkery ◽  
Alex Eustace ◽  
Kathy Gately ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Kinase Inhibitor ◽  
Combined Treatment ◽  
Single Agent ◽  
Src Kinase ◽  
Ic50 Value ◽  
Met Inhibitor ◽  
Dasatinib Treatment

In pre-clinical studies, triple-negative breast cancer (TNBC) cells have demonstrated sensitivity to the multi-targeted kinase inhibitor dasatinib; however, clinical trials with single-agent dasatinib showed limited efficacy in unselected populations of breast cancer, including TNBC. To study potential mechanisms of resistance to dasatinib in TNBC, we established a cell line model of acquired dasatinib resistance (231-DasB). Following an approximately three-month exposure to incrementally increasing concentrations of dasatinib (200 nM to 500 nM) dasatinib, 231-DasB cells were resistant to the agent with a dasatinib IC50 value greater than 5 μM compared to 0.04 ± 0.001 µM in the parental MDA-MB-231 cells. 231-DasB cells also showed resistance (2.2-fold) to the Src kinase inhibitor PD180970. Treatment of 231-DasB cells with dasatinib did not inhibit phosphorylation of Src kinase. The 231-DasB cells also had significantly increased levels of p-Met compared to the parental MDA-MB-231 cells, as measured by luminex, and resistant cells demonstrated a significant increase in sensitivity to the c-Met inhibitor, CpdA, with an IC50 value of 1.4 ± 0.5 µM compared to an IC50 of 6.8 ± 0.2 µM in the parental MDA-MB-231 cells. Treatment with CpdA decreased p-Met and p-Src in both 231-DasB and MDA-MB-231 cells. Combined treatment with dasatinib and CpdA significantly inhibited the growth of MDA-MB-231 parental cells and prevented the emergence of dasatinib resistance. If these in vitro findings can be extrapolated to human cancer treatment, combined treatment with dasatinib and a c-Met inhibitor may block the development of acquired resistance and improve response rates to dasatinib treatment in TNBC.

scholarly journals miR-3188 Regulates Cell Proliferation, Apoptosis, and Migration in Breast Cancer by Targeting TUSC5 and Regulating the p38 MAPK Signaling Pathway

2018 ◽  
Vol 26 (3) ◽  
pp. 363-372 ◽  
Author(s):  
Xiaowen Chen ◽  
Jianli Chen
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Luciferase Reporter ◽  
And Migration ◽  
Mcf 7

This study intended to investigate the effects of miR-3188 on breast cancer and to reveal the possible molecular mechanisms. miR-3188 was upregulated and TUSC5 was downregulated in breast cancer tissues and MCF-7 cells compared to normal tissue and MCF-10 cells. After MCF-7 cells were transfected with miR-3188 inhibitor, cell proliferation and migration were inhibited, whereas apoptosis was promoted. Luciferase reporter assay suggested that TUSC5 was a target gene of miR-3188. In addition, miR-3188 overexpression increased the p-p38 expression, while miR-3188 suppression decreased the p-p38 expression significantly. miR-3188 regulated breast cancer progression via the p38 MAPK signaling pathway. In conclusion, miR-3188 affects breast cancer cell proliferation, apoptosis, and migration by targeting TUSC5 and activating the p38 MAPK signaling pathway. miR-3188 may serve as a potential therapeutic agent for the treatment of breast cancer.

Molecular mechanisms underlying pentabrominated diphenyl ether-induced proliferation in breast cancer MCF-7 cells

2010 ◽  
Vol 92 (6) ◽  
pp. 1177-1185 ◽  
Author(s):  
Yan-Hong Cui ◽  
Ping Zhan ◽  
Dong Luo ◽  
Yin-yin Xia
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Diphenyl Ether ◽  
Mcf 7
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