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 ◽  
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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 Cytotoxic effect of Drimia maritima bulb extract and induction of mitochondrial apoptotic signaling in human breast cancer cells, MCF-7 and MDA-MB-468

2018 ◽  
Vol Volume 11 ◽  
pp. 7669-7677 ◽  
Author(s):  
Maryam Hamzeloo-Moghadam ◽  
Mahmoud Aghaei ◽  
Mohammad Hossein Abdolmohammadi ◽  
Amir Khalaj ◽  
Faranak Fallahian
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Cytotoxic Effect ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Apoptotic Signaling ◽  
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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 ◽  
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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.

Hydroxycitric acid potentiates the cytotoxic effect of tamoxifen in MCF-7 breast cancer cells through inhibition of ATP citrate lyase

Steroids ◽  
2020 ◽  
Vol 160 ◽  
pp. 108656 ◽  
Author(s):  
Ahmed Ismail ◽  
Ahmed S. Doghish ◽  
Bakheet E. M. Elsadek ◽  
Salama A. Salama ◽  
Amr D. Mariee
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cytotoxic Effect ◽  
Atp Citrate Lyase ◽  
Hydroxycitric Acid ◽  
Citrate Lyase ◽  
Mcf 7

scholarly journals Effect of low dose irradiation on estrogen receptor level in MCF-7 breast cancer cells

2001 ◽  
Vol 96 (1) ◽  
pp. 32-40 ◽  
Author(s):  
Daniel Devriendt ◽  
Yan Ma ◽  
Eric Kinnaert ◽  
Fabrice Journe ◽  
Hye-Sook Seo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Low Dose ◽  
Receptor Level ◽  
Dose Irradiation ◽  
Mcf 7

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.

scholarly journals Comparison of the Effects of Resveratrol and Its Derivatives on the Radiation Response of MCF-7 Breast Cancer Cells

2021 ◽  
Vol 22 (17) ◽  
pp. 9511
Author(s):  
Dominika Komorowska ◽  
Agnieszka Gajewska ◽  
Paweł Hikisz ◽  
Grzegorz Bartosz ◽  
Aleksandra Rodacka
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cytotoxic Effect ◽  
Breast Cancer Treatment ◽  
Radiation Response ◽  
Oxygen Species ◽  
Stilbene Derivatives ◽  
Apoptotic Genes ◽  
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Radiotherapy is among the most important methods for breast cancer treatment. However, this method’s effectiveness is limited by radioresistance. The aim of this study was to investigate whether the stilbene derivatives piceid, resveratrol, and piceatannol have a radiosensitising effect on breast cancer cells (MCF-7). The conducted research enabled us to determine which of the tested compounds has the greatest potential in sensitising cells to ionising radiation (IR). Among the stilbene derivatives, resveratrol significantly increased the effect of IR. Resveratrol and IR used in combination had a higher cytotoxic effect on MCF-7 cells than using piceatannol, piceid, or radiation alone. This was due to a significant decrease in the activity of antioxidant enzymes, which resulted in the accumulation of formed reactive oxygen species (ROS). The effect of resveratrol and IR enhanced the expression of apoptotic genes, such as Bax, p53, and caspase 8, leading to apoptosis.

Synergistic cytotoxic effects of tamoxifen and black cohosh on MCF-7 and MDA-MB-231 human breast cancer cells: an in vitro studyThis article is one of a selection of papers published in this special issue (part 2 of 2) on the Safety and Efficacy of Natural Health Products.

2007 ◽  
Vol 85 (11) ◽  
pp. 1153-1159 ◽  
Author(s):  
Mahéra Al-Akoum ◽  
Sylvie Dodin ◽  
Ali Akoum
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cytotoxic Effect ◽  
Black Cohosh ◽  
Proliferative Effect ◽  
Dose Dependent ◽  
Mcf 7

Breast cancer cell cultures were exposed to different concentrations of black cohosh, estradiol (E2), and tamoxifen to examine the effect on cell proliferation; cytotoxicity was assessed by using sulforhodamine B (SRB) dye solution. E2 (10−10–10−8 mol/L) markedly stimulated the proliferation of MCF-7 cells (p < 0.01). Tamoxifen stimulated MCF-7 cell proliferation at 10−6 mol/L and 10−5 mol/L (p < 0.005) but inhibited in a dose-dependent fashion the proliferative effect of E2 (p < 0.001). Black cohosh alone did not show any stimulatory effect, but exhibited a cytotoxic effect, which was significant at 103 μg/mL (p < 0.001). Adding black cohosh at 100–103 μg/mL to E2 at 10−9 mol/L also resulted in a dose-dependent inhibition of E2 proliferative effect. Interestingly, the combination of black cohosh (100–103 μg/mL) with increasing tamoxifen concentrations further inhibited MCF-7 cell growth. On MDA-MB-231 cells, neither E2 nor tamoxifen displayed any detectable effect. However, black cohosh inhibited MDA-MB-231 cell proliferation at 103 μg/mL (p < 0.05), and this inhibitory effect was enhanced by increasing tamoxifen concentrations. This study reveals a cytotoxic effect of black cohosh on both estrogen-sensitive and estrogen-insensitive breast cancer cells and a synergism with tamoxifen for inhibition of cancerous cell growth.

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 ◽  
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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.

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