scholarly journals Doxorubicin–transferrin conjugate alters mitochondrial homeostasis and energy metabolism in human breast cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paulina Wigner ◽  
Krzysztof Zielinski ◽  
Magdalena Labieniec-Watala ◽  
Agnieszka Marczak ◽  
Marzena Szwed
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Mitochondrial Function ◽  
Breast Cancer Cells ◽  
Chemotherapeutic Agents ◽  
Breast Adenocarcinoma ◽  
Breast Cancer Cell Lines ◽  
Antioxidant Systems ◽  
Exact Nature ◽  
Human Breast

AbstractDoxorubicin (DOX) is considered one of the most powerful chemotherapeutic agents but its clinical use has several limitations, including cardiomyopathy and cellular resistance to the drug. By using transferrin (Tf) as a drug carrier, however, the adverse effects of doxorubicin as well as drug resistance can be reduced. The main objective of this study was to determine the exact nature and extent to which mitochondrial function is influenced by DOX–Tf conjugate treatment, specifically in human breast adenocarcinoma cells. We assessed the potential of DOX–Tf conjugate as a drug delivery system, monitoring its cytotoxicity using the MTT assay and ATP measurements. Moreover, we measured the alterations of mitochondrial function and oxidative stress markers. The effect of DOX–Tf was the most pronounced in MDA-MB-231, triple-negative breast cancer cells, whereas non-cancer endothelial HUVEC-ST cells were more resistant to DOX–Tf conjugate than to free DOX treatment. A different sensitivity of two investigate breast cancer cell lines corresponded to the functionality of their cellular antioxidant systems and expression of estrogen receptors. Our data also revealed that conjugate treatment mediated free radical generation and altered the mitochondrial bioenergetics in breast cancer cells.

The Impact of Antioxidants from the Diet on Breast Cancer Cells Monitored by Raman Microspectroscopy

2018 ◽  
Vol 16 (2) ◽  
pp. 127-137
Author(s):  
Paula Sofia Coutinho Medeiros ◽  
Ana Lúcia Marques Batista de Carvalho ◽  
Cristina Ruano ◽  
Juan Carlos Otero ◽  
Maria Paula Matos Marques
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Breast Adenocarcinoma ◽  
Coumaric Acid ◽  
Human Breast ◽  
The Impact

Background: The impact of the ubiquitous dietary phenolic compound p-coumaric acid on human breast cancer cells was assessed, through a multidisciplinary approach: Combined biological assays for cytotoxicity evaluation and biochemical profiling by Raman microspectroscopic analysis in cells. </P><P> Methods: Para-coumaric acid was shown to exert in vitro chemoprotective and antitumor activities, depending on the concentration and cell line probed: a significant anti-invasive ability was detected for the triple-negative MDA-MB-231 cells, while a high pro-oxidant effect was found for the estrogen- dependent MCF-7 cells. A striking cell selectivity was obtained, with a more noticeable outcome on the triple-negative MDA-MB-231 cell line. Results: The main impact on the cellular biochemical profile was verified to be on proteins and lipids, thus justifying the compound´s anti-invasive effect and chemoprotective ability. Conclusion: p-Coumaric acid was thus shown to be a promising chemoprotective/chemotherapeutic agent, particularly against the low prognosis triple-negative human breast adenocarcinoma.

scholarly journals ARTEMISININ MODULATING EFFECT ON HUMAN BREAST CANCER CELL LINES WITH DIFFERENT SENSITIVITY TO CYTOSTATICS

2017 ◽  
Vol 39 (1) ◽  
pp. 25-29 ◽  
Author(s):  
V F Chekhun ◽  
N Yu Lukianova ◽  
T Borikun ◽  
T Zadvornyi ◽  
A Mokhir
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Iron Homeostasis ◽  
Chemotherapeutic Agents ◽  
Fold Change ◽  
Breast Cancer Cell Lines ◽  
Cellular Iron ◽  
Mcf 7

Aim: To explore effects of Artemisinin on a series of breast cancer cells with different sensitivity to typical cytotoxic drugs (doxorubicin — Dox; cisplatin — DDP) and to investigate possible artemisinin-induced modification of the mechanisms of drug resistance. Materials and Methods: The study was performed on wild-type breast cancer MCF-7 cell line (MCF-7/S) and its two sublines MCF-7/Dox and MCF-7/DDP resistant to Dox and DDP, respectively. The cells were treated with artemisinin and iron-containing magnetic fluid. The latter was added to modulate iron levels in the cells and explore its role in artemisinin-induced effects. The MTT assay was used to monitor cell viability, whereas changes of expression of selected proteins participating in regulation of cellular iron homeostasis were estimated using immunocytochemical methods. Finally, relative expression levels of miRNA-200b, -320a, and -34a were examined by using qRT-PCR. Results: Artemisinin affects mechanisms of the resistance of breast cancer cells towards both Dox and DDP at sub-toxic doses. The former drug induces changes of expression of iron-regulating proteins via different mechanisms, including epigenetic regulation. Particularly, the disturbances in ferritin heavy chain 1, lactoferrin, hepcidin (decrease) and ferroportin (increase) expression (р ≤ 0.05) were established. The most enhanced increase of miRNA expression under artemisinin influence were found for miRNA-200b in MCF-7/DDP cells (7.1 ± 0.98 fold change), miRNA-320a in MCF-7/Dox cells (2.9 ± 0.45 fold change) and miRNA-34a (1.7 ± 0.15 fold change) in MCF-7/S cells. It was observed that the sensitivity to artemisinin can be influenced by changing iron levels in cells. Conclusions: Artemisinin can modify iron metabolism of breast cancer cells by its cytotoxic effect, but also by inducing changes in expression of iron-regulating proteins and microRNAs (miRNAs), involved in their regulation. This modification affects the mechanisms that are implicated in drug-resistance, that makes artemisinin a perspective modulator of cell sensitivity towards chemotherapeutic agents in cancer treatment.

Antagonism of chemotherapy-induced cytotoxicity for human breast cancer cells by antiestrogens.

1989 ◽  
Vol 7 (6) ◽  
pp. 710-717 ◽  
Author(s):  
C K Osborne ◽  
L Kitten ◽  
C L Arteaga
Keyword(s):  
Breast Cancer ◽  
Drug Interaction ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Additive Interaction ◽  
Er Positive ◽  
Cultured Liver Cells

In a prior National Surgical Adjuvant Breast and Bowel Project (NSABP) adjuvant study, the addition of the antiestrogen tamoxifen to chemotherapy with melphalan and fluorouracil adversely affected survival in several patient subsets, suggesting an antagonistic drug interaction. To investigate this possibility, we studied the interaction of tamoxifen and other antiestrogens with several cytotoxic drugs in cultured human breast cancer cell lines. Clinically relevant concentrations of tamoxifen and melphalan reduced colony survival of estrogen receptor (ER)-positive breast cancer cells when used alone in a colony-forming assay. However, pretreatment of cells with tamoxifen followed by exposure to melphalan resulted in antagonism, with more colonies surviving treatment with the combination than with melphalan alone. Identical effects were seen using several other triphenylethelene antiestrogens. An antagonistic interaction was observed even with a brief preincubation with tamoxifen that had no effect on cell proliferation, indicating that antagonism was not due to tamoxifen's known cell kinetic effects. Tamoxifen even antagonized melphalan cytotoxicity in ER-negative breast cancer cells and in cultured liver cells. An additive drug interaction occurred when melphalan was combined with pharmacologic concentrations of estradiol or medroxyprogesterone acetate, but antagonism was also observed with dexamethasone. Tamoxifen also antagonized the cytotoxicity of fluorouracil in these cells. However, an additive interaction occurred when the antiestrogen was combined with doxorubicin or 4-hydroxy-cyclophosphamide, an alkylating agent that is transported into the cell by a different carrier-mediated mechanism than melphalan. To avoid potential antagonism in the clinic, combinations of tamoxifen with melphalan and/or fluorouracil should be avoided.

scholarly journals A Combination of an Antimitotic and a Bromodomain 4 Inhibitor Synergistically Inhibits the Metastatic MDA-MB-231 Breast Cancer Cell Line

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Thandi Mqoco ◽  
André Stander ◽  
Anna-Mart Engelbrecht ◽  
Anna M Joubert
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Chemotherapeutic Agents ◽  
Breast Cancer Cell Lines ◽  
Mcf 7

Current chemotherapeutic agents have many side effects and are toxic to normal cells, providing impetus to identify agents that can effectively eliminate tumorigenic cells without damaging healthy cells. The aim of this study was to examine whether combining a novel BRD4 inhibitor, ITH-47, with the antimitotic estradiol analogue, ESE-15-ol, would have a synergistic effect on inhibiting the growth of two different breast cancer cell lines in vitro. Our docking and molecular dynamics studies showed that compared to JQ1, ITH-47 showed a similar binding mode with hydrogen bonds forming between the ligand nitrogens of the pyrazole, ASN99, and water of the BRD4 protein. Data from cell growth studies revealed that the GI50 of ITH-47 and ESE-15-ol after 48 hours of exposure was determined to be 15 μM and 70 nM, respectively, in metastatic MDA-MB-231 breast cancer cells. In tumorigenic MCF-7 breast cancer cells, the GI50 of ITH-47 and ESE-15-ol was 75 μM and 60 nM, respectively, after 48 hours of exposure. Furthermore, the combination of 7.5 μM and 14 nM of ITH-47 and ESE-15-ol, respectively, resulted in 50% growth inhibition of MDA-MB-231 cells resulting in a synergistic combination index (CI) of 0.7. Flow cytometry studies revealed that, compared to the control, combination-treated MDA-MB-231 cells had significantly more cells present in the sub-G1 phase and the combination treatment induced apoptosis in the MDA-MB-231 cells. Compared to vehicle-treated cells, the combination-treated cells showed decreased levels of the BRD4, as well as c-Myc protein after 48 hours of exposure. In combination, the selective BRD4 inhibitor, ITH-47, and ESE-15-ol synergistically inhibited the growth of MDA-MB-231 breast cancer cells, but not of the MCF-7 cell line. This study provides evidence that resistance to BRD4 inhibitors may be overcome by combining inhibitors with other compounds, which may have treatment potential for hormone-independent breast cancers.

scholarly journals Specific downregulation of bcl-2 and xIAP by RNAi enhances the effects of chemotherapeutic agents in MCF-7 human breast cancer cells

2004 ◽  
Vol 11 (5) ◽  
pp. 309-316 ◽  
Author(s):  
Raquel T Lima ◽  
Luís M Martins ◽  
José E Guimarães ◽  
Clara Sambade ◽  
M Helena Vasconcelos
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Chemotherapeutic Agents ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Mcf 7

scholarly journals Osteoblast-conditioned medium promotes proliferation and sensitizes breast cancer cells to imatinib treatment

2007 ◽  
Vol 14 (1) ◽  
pp. 61-72 ◽  
Author(s):  
Marina Brama ◽  
Sabrina Basciani ◽  
Sara Cherubini ◽  
Stefania Mariani ◽  
Silvia Migliaccio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tyrosine Kinase ◽  
Cancer Cells ◽  
Conditioned Medium ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines ◽  
Imatinib Treatment ◽  
Human Breast ◽  
Mcf 7

Inhibition of platelet-derived growth factor receptor (PDGFR) signaling restricts the growth of human breast cancer in the bone of nude mice. We hypothesized that osteoblast-secreted substances may alter the response capacity of breast cancer cells to the PDGFRs tyrosine kinase inhibitor imatinib mesylate. We found that osteoblast-conditioned medium (OCM) increases the proliferation rate of the estrogen receptor negative (ER−) MDA-MB-231 and of the ER+ MCF-7 human breast cancer cell lines and the growth-promoting effect on ER+ cells is independent from estrogen. OCM significantly improved the dose- and the time-dependent sensitivity of the tumor cells to the anti-proliferative effect of imatinib. We also found that MDA-MB-231 and MCF-7 cells express the two PDGFRs subtypes, PDGFR-α and PDGFR-β, and OCM treatment increases the expression of the PDGFRs. Furthermore, imatinib inhibited the phosphorylation rate of its target tyrosine kinase receptors. We conclude that bone microenvironment, through osteoblast-secreted substances may cause estrogen-independent proliferation of breast cancer cells by a mechanism mediated by the induction of PDGFRs expression. The enhanced sensitivity of OCM-treated breast cancer cells to imatinib would justify investigation on the efficacy of imatinib in bone breast cancer metastasis.

scholarly journals Impact of ethanolic extract of Mikania glomerata on human breast cancer (MCF 7) cell line

2016 ◽  
Vol 2 (4) ◽  
pp. 94 ◽  
Author(s):  
Sarojini S. ◽  
Senthilkumaar P. ◽  
Ramesh V.
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Ethanolic Extract ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Anti Cancer ◽  
Mikania Glomerata ◽  
Mcf 7

The ethanol extract of Mikania glomerata has anti-proliferative effect on the human breast cancer cell lines. The object of the present work is to investigate the anti-cancer effect of Mikania glomerata ethanolic extract on breast cancer. Soxlet fractions using crude ethanolic extract of Mikania glomerata was prepared by standard extraction protocols. To check the antiproliferative effect of this extract, the extract chosen was tested for cell viability on the breast cancer cells MCF 7 in different concentrations. Cell viability was evaluated by MTT assay for 24 hour and 48 hours. The LD50 value was calculated and different morphometric assays were performed with the effective dose of the extract. The effect of the extract on the normal cell was evaluated as well. Cell proliferation, cell cycle, Clonogenic survival, Apoptosis and MTT assays were performed. The ethanolic extract showed a dose-dependent and time dependent inhibition on cell proliferation in the breast cancer cell lines. It showed low cytotoxicity in the normal cells and inhibited cellular adhesion and wound healing in treated cancer cells. The present study suggests that the leaf extract from Mikania glomerata induces anticancer effect on the breast cancer cells. Further study might help to confirm it as an anti-cancer drug.

scholarly journals Dovitinib Triggers Apoptosis and Autophagic Cell Death by Targeting SHP-1/p-STAT3 Signaling in Human Breast Cancers

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Yi-Han Chiu ◽  
Yi-Yen Lee ◽  
Kuo-Chin Huang ◽  
Cheng-Chi Liu ◽  
Chen-Si Lin
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Ectopic Expression ◽  
Health Concern ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Human Breast ◽  
Stat3 Inhibition

Breast cancer is the most common cancer and the leading cause of cancer deaths in women worldwide. The rising incidence rate and female mortality make it a significant public health concern in recent years. Dovitinib is a novel multitarget receptor tyrosine kinase inhibitor, which has been enrolled in several clinical trials in different cancers. However, its antitumor efficacy has not been well determined in breast cancers. Our results demonstrated that dovitinib showed significant antitumor activity in human breast cancer cell lines with dose- and time-dependent manners. Downregulation of phosphor-(p)-STAT3 and its subsequent effectors Mcl-1 and cyclin D1 was responsible for this drug effect. Ectopic expression of STAT3 rescued the breast cancer cells from cell apoptosis induced by dovitinib. Moreover, SHP-1 inhibitor reversed the downregulation of p-STAT3 induced by dovitinib, indicating that SHP-1 mediated the STAT3 inhibition effect of dovitinib. In addition to apoptosis, we found for the first time that dovitinib also activated autophagy to promote cell death in breast cancer cells. In conclusion, dovitinib induced both apoptosis and autophagy to block the growth of breast cancer cells by regulating the SHP-1-dependent STAT3 inhibition.

Anticancer Potential of Pulicaria crispa Extract on Human Breast Cancer MDA-MB-231 Cells

2019 ◽  
Vol 16 (12) ◽  
pp. 1354-1359
Author(s):  
Ibrahim Omar Barnawi ◽  
Imran Ali
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Soxhlet Extraction ◽  
Breast Cancer Cell Lines ◽  
Cell Integrity ◽  
Human Breast ◽  
Excessive Sweating ◽  
Morphological Alterations

Background: Breast cancer is the common cause of deaths among women globally with 15% mortality globally. Introduction: Today, about 80% of the rural population depends on natural products as primary health care. Pulicaria crispa (L., family Compositae) is utilized in traditional medicine for curing colds, coughs, colic, and excessive sweating and as a carminative. Methods: The extracts of Pulicaria crispa; grown in Saudi Arabia; were assessed to measure the cytotoxicity with MDA-MB-231 breast cancer cell lines. Soxhlet extraction was utilized for stem, leaves and flower with 70% ethanol. The cytotoxicity of the extracts with MDA-MB-231 breast cancer cells was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Results: The apoptotic cellular morphological alterations were detected by fluorescence microscopes. The results indicated that Pulicaria crispa exhibited a strong anticancer activity with a halfmaximal inhibitory concentration (IC50) of 180 µg/mL against breast cancer cells. The loss in cell integrity, shrinkage of cytoplasm, and cell detachment were seen in the extract treated with MDAMB- 231 cells. The cell death was due to membrane destruction. Conclusion: Pulicaria crispa extracts indicated significant cytotoxicity against human breast cancer cells (MDA-MB-231 cells). The extract of this plant may be given to the patients having breast cancer.

Determination of Vulpinic Acid Effect on Apoptosis and mRNA Expression Levels in Breast Cancer Cell Lines

2019 ◽  
Vol 18 (14) ◽  
pp. 2032-2041 ◽  
Author(s):  
Nil Kılıç ◽  
Sümer Aras ◽  
Demet Cansaran-Duman
Keyword(s):  
Breast Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines ◽  
Human Breast

Objective: Breast cancer is one of the most common diseases among women worldwide and it is characterized by a high ratio of malignancy and metastasis and low rate of survival of patients. Due to limited treatment options, the discovery of alternative therapeutic agents and clarifying the molecular mechanism of breast cancer development may offer new hope for its treatment. Lichen secondary metabolites may be one of these therapeutic agents. Methods: In this study, the effects of Vulpinic Acid (VA) lichen secondary metabolite on the cell viability and apoptosis of breast cancer cells and non-cancerous cell line were investigated. Quantitative polymerase chain reaction was also performed to determine changes in the expression of apoptosis-related genes at a molecular level. Results: The results demonstrated that VA significantly inhibited the cell viability and induced apoptosis of human breast cancer cells. The highest rates of decreased growth were determined using the IC50 value of VA for 48h on MCF-7 breast cancer cell. Interestingly, VA treatment significantly reduced cell viability in all examined breast cancer cell lines compared to their non-cancerous human breast epithelial cell line. This is the first study on the investigation of the effects of VA on the molecular mechanisms associated with the expression of apoptosis-related genes in breast cancer cell lines. Results demonstrated that the gene expression of P53 genes was altered up to fourteen-fold levels in SK-BR-3 cell lines whereas it reached 2.5-fold in the MCF-12A cell line after treatment with VA. These observations support that VA induces apoptosis on the breast cancer cells compared with the non-cancerous human breast epithelial cell line. Conclusion: It is implicated that VA may be a promising novel molecule for the induction of apoptosis on breast cancer cells.

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