scholarly journals Micronutrients Selenomethionine and Selenocysteine Modulate the Redox Status of MCF-7 Breast Cancer Cells

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 865 ◽  
Author(s):  
Daniel Gabriel Pons ◽  
Carmen Moran ◽  
Marina Alorda-Clara ◽  
Jordi Oliver ◽  
Pilar Roca ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hydrogen Peroxide ◽  
Antioxidant Enzymes ◽  
Protein Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Redox Status ◽  
Hydrogen Peroxide Production ◽  
Low Concentrations ◽  
Mcf 7

Selenium is a micronutrient which is found in many foods, with redox status modulation activity. Our aim was to evaluate the effects of two chemical forms of selenoamino acids, Seleno-L-methionine and Seleno-L-cystine (a diselenide derived from selenocysteine), at different concentrations on cell viability, hydrogen peroxide production, antioxidant enzymes, UCP2 protein expression, as well as lipid and protein oxidative damage in MCF-7 breast cancer cells. Results showed that Seleno-L-methionine did not cause an increase in hydrogen peroxide production at relatively low concentrations, accompanied by a rise in the antioxidant enzymes catalase and MnSOD, and UCP2 protein expression levels. Furthermore, a decrease in protein and lipid oxidative damage was observed at 10 µM concentration. Otherwise, Seleno-L-cystine increased hydrogen peroxide production from relatively low concentrations (100 nM) to a large increase at high concentrations. Moreover, at 10 µM, Seleno-L-cystine decreased UCP2 and MnSOD protein expression. In conclusion, the chemical form of selenoamino acid and their incorporation to selenoproteins could affect the regulation of the breast cancer cell redox status. Taken together, the results obtained in this study imply that it is important to control the type of selenium-enriched nutrient consumption, taking into consideration their composition and concentration.

scholarly journals Inhibition of STAT3 enhances sensitivity to tamoxifen in tamoxifen-resistant breast cancer cells

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Seo Yun Moon ◽  
Heejin Lee ◽  
Seoree Kim ◽  
Ji Hyung Hong ◽  
Sang Hoon Chun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Signalling Pathway ◽  
Expression Levels ◽  
Er Positive ◽  
Tamoxifen Resistant ◽  
Stat3 Signalling ◽  
Mcf 7

Abstract Background The mechanisms of endocrine resistance are complex, and deregulation of several oncogenic signalling pathways has been proposed. We aimed to investigate the role of the EGFR and Src-mediated STAT3 signalling pathway in tamoxifen-resistant breast cancer cells. Methods The ER-positive luminal breast cancer cell lines, MCF-7 and T47D, were used. We have established an MCF-7-derived tamoxifen-resistant cell line (TamR) by long-term culture of MCF-7 cells with 4-hydroxytamoxifen. Cell viability was determined using an MTT assay, and protein expression levels were determined using western blot. Cell cycle and annexin V staining were analysed using flow cytometry. Results TamR cells showed decreased expression of estrogen receptor and increased expression of EGFR. TamR cells showed an acceleration of the G1 to S phase transition. The protein expression levels of phosphorylated Src, EGFR (Y845), and STAT3 was increased in TamR cells, while phosphorylated Akt was decreased. The expression of p-STAT3 was enhanced according to exposure time of tamoxifen in T47D cells, suggesting that activation of STAT3 can cause tamoxifen resistance in ER-positive breast cancer cells. Both dasatinib (Src inhibitor) and stattic (STAT3 inhibitor) inhibited cell proliferation and induced apoptosis in TamR cells. However, stattic showed a much stronger effect than dasatinib. Knockdown of STAT3 expression by siRNA had no effect on sensitivity to tamoxifen in MCF-7 cells, while that enhanced sensitivity to tamoxifen in TamR cells. There was not a significant synergistic effect of dasatinib and stattic on cell survival. TamR cells have low nuclear p21(Cip1) expression compared to MCF-7 cells and inhibition of STAT3 increased the expression of nuclear p21(Cip1) in TamR cells. Conclusions The EGFR and Src-mediated STAT3 signalling pathway is activated in TamR cells, and inhibition of STAT3 may be a potential target in tamoxifen-resistant breast cancer. An increase in nuclear p21(Cip1) may be a key step in STAT3 inhibitor-induced cell death in TamR cells.

Anti-carcinogenic effect of Cathepsin K Inhibitor, Odanacatib with low dose of Cisplatin Against Human Breast Carcinoma MCF-7 and MDAMB231 Cells

2020 ◽  
Vol 16 ◽  
Author(s):  
Yaongamphi Vashum ◽  
Amuthavalli Kottaiswamy ◽  
Tholcopiyan Loganathan ◽  
Fathima Bushra Sheriff ◽  
Shila Samuel
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cytotoxic Effect ◽  
Low Dose ◽  
Cathepsin K ◽  
Platinum Compound ◽  
Alternative Treatment Option ◽  
Mcf 7

Background: A cross-linking agent commonly used for cancer chemotherapy is a platinum compound such as cisplatin. However, with the acquisition of cellular drug resistance and adverse side effects, the potency of cisplatin is therefore, often tempered. To overcome these, the present study has established the use of cathepsin k (CTSK) inhibitor as a potent chemo sensitizer. Methods: The cytotoxic effect of cisplatin and odanacatib (ODN) on two different breast cancer patient-derived cell lines, MDA-MB-231 and MCF-7, was assessed by MTT-based colorimetric assay. The drug interaction coefficient CDI was used to evaluate the synergistically inhibitory impact of the drug combination and immunoblot was used to examine protein expression of certain proteins responsible for cell survival and the mechanism of apoptosis. Results: In this study, we found that IC50 of ODN in combination with cisplatin (half of IC25) induces a synergistic cytotoxic effect in different breast cancer cells. Diminished expression of Bcl-2 and increased expression of Bax aroused the cytochrome release, that triggers caspase-9 and -3 activation in the combinatorial group. ODN with lower dose of cisplatin significantly inhibits the protein expression of novel chemoresistant factors such as STAT3, NFҡB and IL-6. Conclusion: This study highlights the potential effects of the combination of ODN with reduced dose of cisplatin on improving the growth inhibition and apoptosis-inducing effect on breast cancer cells via combined inhibition of NF-κBinduced IL-6 and STAT3 activation.The study result suggests that the further development of this novel inhibitor combination with low dose of standard cisplatin-based chemotherapy may contribute to alternative treatment option for certain cancers.

scholarly journals All trans-retinoic acid acts synergistically with hydroxytamoxifen and transforming-growth factor β to stimulate apoptosis in MCF-7 breast cancer cells

2004 ◽  
Vol 183 (2) ◽  
pp. 395-404 ◽  
Author(s):  
D N Danforth
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Protein Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Transforming Growth Factor ◽  
Synergistic Effects ◽  
Transforming Growth Factor Β ◽  
Mcf 7

The anti-estrogen 4-hydroxytamoxifen (TAM) and vitamin A-related compounds, the retinoids, in combination act synergistically to inhibit growth of breast cancer cells in vitro and in vivo. To clarify the mechanism of this synergism, the effect of TAM and all trans-retinoic acid (AT) on proliferation of MCF-7 breast cancer cells was studied in vitro. TAM and AT acted synergistically to cause a time-dependent and dose-dependent inhibition of MCF-7 cell growth. In a temporally related manner, TAM+AT acted synergistically to downregulate Bcl-2 mRNA and Bcl-2 protein expression, and to stimulate apoptosis. TAM and AT each blocked cell cycle progression throughout 7 days of treatment but without any synergistic or additive effect on this process, indicating a selective synergism for apoptosis. The negative growth factor-transforming growth factor β (TGFβ) is secreted by these cells and was studied as a potential mediator of the synergistic effects of TAM+AT on apoptosis. TAM+AT acted synergistically to induce a fivefold increase in TGFβ1 secretion over 72 h. TGFβ1 alone had no apoptotic effects on these cells; however, TGFβ1 in combination with AT acted synergistically to inhibit growth, to downregulate Bcl-2 mRNA and Bcl-2 protein expression, and to stimulate apoptosis of these cells in a manner comparable with that noted for TAM+AT. The synergism of both TAM+AT and TGFβ1+AT for apoptosis was suppressed by estradiol. Co-incubation of TAM+AT with anti-TGFβ antibody did not block down-regulation of Bcl-2 protein expression or stimulation of apoptosis. The synergistic effects of TAM+AT on apoptosis therefore occur independently of TGFβ, although TGFβ may interact with AT in a novel manner to provide another important anti-proliferative mechanism for breast cancer cells.

scholarly journals The Inhibitory Effect of Cordycepin on the Proliferation of MCF-7 Breast Cancer Cells, and Its Mechanism: An Investigation Using Network Pharmacology-Based Analysis

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 414 ◽  
Author(s):  
Dahae Lee ◽  
Won-Yung Lee ◽  
Kiwon Jung ◽  
Yong Kwon ◽  
Daeyoung Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Brown Rice ◽  
Gene Set Enrichment Analysis ◽  
Inhibitory Effects ◽  
Anticancer Effects ◽  
Ic50 Value ◽  
Mcf 7

Cordyceps militaris is a well-known medicinal mushroom. It is non-toxic and has clinical health benefits including cancer inhibition. However, the anticancer effects of C. militaris cultured in brown rice on breast cancer have not yet been reported. In this study, we simultaneously investigated the anticancer effects of cordycepin and an extract of C. militaris cultured in brown rice on MCF-7 human breast cancer cells using a cell viability assay, cell staining with Hoechst 33342, and an image-based cytometric assay. The C. militaris concentrate exhibited significant MCF-7 cell inhibitory effects, and its IC50 value was 73.48 µg/mL. Cordycepin also exhibited significant MCF-7 cell inhibitory effects, and its IC50 value was 9.58 µM. We applied network pharmacological analysis to predict potential targets and pathways of cordycepin. The gene set enrichment analysis showed that the targets of cordycepin are mainly associated with the hedgehog signaling, apoptosis, p53 signaling, and estrogen signaling pathways. We further verified the predicted targets related to the apoptosis pathway using western blot analysis. The C. militaris concentrate and cordycepin exhibited the ability to induce apoptotic cell death by increasing the cleavage of caspase-7 -8, and -9, increasing the Bcl-2-associated X protein/ B-cell lymphoma 2 (Bax/Bcl-2) protein expression ratio, and decreasing the protein expression of X-linked inhibitor of apoptosis protein (XIAP) in MCF-7 cells. Consequently, the C. militaris concentrate and cordycepin exhibited significant anticancer effects through their ability to induce apoptosis in breast cancer cells.

scholarly journals Paeoniflorin Enhances the Sensitivity of ER-Positive Breast Cancer Cells to Tamoxifen through Promoting Sirtuin 4

2022 ◽  
Vol 2022 ◽  
pp. 1-11
Author(s):  
Pei Zhang ◽  
Nan Wu ◽  
Zhi-Jun Song ◽  
Zheng-Fu Tai
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Protein Expression ◽  
Cancer Cells ◽  
Cell Lines ◽  
Breast Cancer Cells ◽  
Expression Ratio ◽  
Er Positive ◽  
Mcf 7 ◽  
Positive Breast Cancer

Tamoxifen is an effective drug for treating patients with advanced estrogen receptor-positive (ER+) breast cancer (BC), but not for all ER + BC patients. Drug tolerance is the biggest obstacle. In this study, we designed an experiment to investigate whether paeoniflorin affects the ER + BC cell’s sensitivity to tamoxifen in the T47D and MCF-7 cell lines. Herein, we found that paeoniflorin inhibited cell proliferation without inducing apoptosis. However, it enhanced tamoxifen-induced apoptosis in both cell lines. Immunoblotting revealed that paeoniflorin significantly increased the already elevated Bax/Bcl2 protein expression ratio and the caspase 3 activity levels, both induced by tamoxifen. Paeoniflorin was also found to increase SIRT4 expression, and deletion of SIRT4 could significantly reverse the inhibition of cell proliferation induced by paeoniflorin and significantly decrease paeoniflorin-enhanced apoptosis induced by tamoxifen. Moreover, protein expression detection revealed that paeoniflorin enhanced the tamoxifen-induced inhibition of STAT3 activation. Besides, the deletion of SIRT4 could significantly increase STAT3 activation in the T47D and MCF-7 cells. In conclusion, paeoniflorin suppressed STAT3 activation to enhance the sensitivity of ER-positive breast cancer cells to tamoxifen through promoting SIRT4 expression.

scholarly journals Decreas of BCL-2 Expression by Ethanol Extract of Ocinum basilicum L. Leaves in Breast Cancer Cells

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Devi Nisa Hidayati ◽  
Fatimatuz Zahroh ◽  
Lina Wahyuni ◽  
Ibrahim Arifin
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Protein Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Ethanol Extract ◽  
Ocimum Basilicum ◽  
Protein Expressions ◽  
Mcf 7

Ocimum basilicum L has proven to have in vitro cytotoxic activity against breast cancer cells. Pathways that cause cell death can involve one of the proteins, which is BCL-2. This study aims to determine the decrease of BCL-2 protein expressions in breast cancer cells (T47D and MCF-7) tat are treated with the ethanol extract of Ocimum basilicum L. Ocimum basilicum L. was extracted using the maceration method with 70% ethanol solvent. The concentration of ethanol extract of Ocimum basilicum L. used to see the expression of BCL-2 protein in T47D and MCF-7 cells was 199 µg/ml and 388 µg / mL. The observation of BCL-2 protein expression is using immunocytochemical methods of T47D and MCF-7 cancer cells. The results showed that the ethanol extract of Ocimum basilicum L could reduce BCL-2 protein expression in breast cancer cells (T47D and MCF-7) at concentrations of 199 µg/ml and 388 µg/ml, respectively.

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