Metformin Resistant MDA-MB-468 Cells Exhibit EMT-like Phenotype and Increased Migration Capacity

2021 ◽  
Author(s):  
şahika cıngır köker ◽  
Banu Yalcin ◽  
İrem Dogan Turacli
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Mcf7 Cells ◽  
Protein Levels ◽  
Positive Effects ◽  
Proliferative Effect ◽  
Metastatic Behavior ◽  
Migration Capacity

Abstract Purpose: Metformin is one of the most prescribed drug for the treatment of type II diabetes. Its anti-proliferative effect is also taken advantage for the treatment of cancer. Despite many of the studies mention the positive effects of metformin in inhibiting the proliferation of cancer cells, there are also studies which questions this idea as well.Methods: In this study, we investigated the most widely studied breast cancer cell lines, ER(+) MCF7 cells, TNBC MDA-MB-231 and MDA-MB468 cells in terms of metastatic behavior under long-term metformin treatment. MCF7, MDA-MB231 and MDA-MB468 cells were gained resistant to metformin starting from 0.2mM to 3.2mM. Results: Compared to MCF7 and MDA-MB231 cell lines, we only observed dramatic changes in MDA-MB468 cells whose morphology has been changed towards mesenchymal like phenotype. Moreoever, migration capacity of these cells were also significanlty increased which were validated at both mRNA and protein levels as well as wound healing assay. In addition EMT like phenotype and increasing migration capacity of metformin resistant MDA-MB468 cells, they exhibited less sensitivity to PI3K inhibitor. Conclusions: All together, our data pointed out that, metformin’s effects should be questioned depending on the subtype of the breast cancer that’s to be treated.

scholarly journals Metformin Resistant MDA-MB-468 Cells Exhibit EMT-like Phenotype and Increased Migration Capacity

2021 ◽  
Author(s):  
Sahika Cingir Koker ◽  
Banu Yalcin ◽  
Irem Dogan Turacli
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Mcf7 Cells ◽  
Protein Levels ◽  
Positive Effects ◽  
Proliferative Effect ◽  
Metastatic Behavior ◽  
Migration Capacity

Abstract Background: Metformin is one of the most prescribed drug for the treatment of type II diabetes. Its anti-proliferative effect is also taken advantage for the treatment of cancer. Despite many of the studies mention the positive effects of metformin in inhibiting the proliferation of cancer cells, there are also studies which questions this idea as well.Methods: In this study, we investigated the most widely studied breast cancer cell lines, ER(+) MCF7 cells, TNBC MDA-MB-231 and MDA-MB468 cells in terms of metastatic behavior under long-term metformin treatment. MCF7, MDA-MB231 and MDA-MB468 cells were gained resistant to metformin starting from 0.2mM to 3.2mM. Results: Compared to MCF7 and MDA-MB231 cell lines, we only observed dramatic changes in MDA-MB468 cells whose morphology has been changed towards mesenchymal like phenotype. Moreoever, migration capacity of these cells were also significanlty increased which were validated at both mRNA and protein levels as well as wound healing assay. In addition EMT like phenotype and increasing migration capacity of metformin resistant MDA-MB468 cells, they exhibited less sensitivity to PI3K inhibitor. Conclusions: All together, our data pointed out that, metformin’s effects should be questioned depending on the subtype of the breast cancer that’s to be treated.

Modulation of Cathepsin-D and pS2 Protein Levels in Human Breast Cancer Cell Lines

Tumor Biology ◽  
1996 ◽  
Vol 17 (5) ◽  
pp. 290-298 ◽  
Author(s):  
V. Cappelletti ◽  
L. Fioravanti ◽  
P. Miodini ◽  
G. Di Fronzo
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Breast Cancer Cell ◽  
Cathepsin D ◽  
Human Breast Cancer ◽  
Human Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Protein Levels ◽  
Ps2 Protein

scholarly journals Trastuzumab in combination with AT-101 induces cytotoxicity and apoptosis in Her2 positive breast cancer cells

2020 ◽  
Vol 16 (3) ◽  
pp. 4485-4495
Author(s):  
Gulcan Bulut ◽  
Harika Atmaca ◽  
Burcak Karaca
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines ◽  
Her2 Positive ◽  
Protein Levels ◽  
Her2 Positive Breast Cancer ◽  
Synergistic Cytotoxicity ◽  
Positive Breast Cancer

Aim: AT-101 is a polyphenolic compound with potent anti-apoptotic effects in various cancers. In this study, the possible synergistic cytotoxic and apoptotic effect of trastuzumab/AT-101 combination was investigated in HER2-positive breast cancer cell lines. Materials & methods: SKBR-3, MDA-MB-453 and MCF-10A cell lines were treated with a trastuzumab/AT-101 combination. Synergistic cytotoxicity and apoptosis effects were shown and then PI3K and Akt protein levels were studied. Result: The trastuzumab/AT-101 combination induced synergistic cytotoxicity and apoptosis in both breast cancer cells but not in MCF-10A cells. Combination treatment induced cytotoxicity via inhibiting PI3K/AKT but not the MAPK/ERK pathway. Conclusion: The trastuzumab/AT-101 combination may be a good candidate for patients with trastuzumab-resistant Her2-positive breast cancer and inhibition of the PI3K/AKT pathway may be one of the underlying mechanisms.

scholarly journals Matrix Metalloproteinase 8 (Collagenase 2) Induces the Expression of Interleukins 6 and 8 in Breast Cancer Cells

2013 ◽  
Vol 288 (23) ◽  
pp. 16282-16294 ◽  
Author(s):  
Sally Thirkettle ◽  
Julie Decock ◽  
Hugh Arnold ◽  
Caroline J. Pennington ◽  
Diane M. Jaworski ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Matrix Metalloproteinase ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines

Matrix metalloproteinase 8 (MMP-8) is a tumor-suppressive protease that cleaves numerous substrates, including matrix proteins and chemokines. In particular, MMP-8 proteolytically activates IL-8 and, thereby, regulates neutrophil chemotaxis in vivo. We explored the effects of expression of either a WT or catalytically inactive (E198A) mutant version of MMP-8 in human breast cancer cell lines. Analysis of serum-free conditioned media from three breast cancer cell lines (MCF-7, SK-BR-3, and MDA-MB-231) expressing WT MMP-8 revealed elevated levels of IL-6 and IL-8. This increase was mirrored at the mRNA level and was dependent on MMP-8 catalytic activity. However, sustained expression of WT MMP-8 by breast cancer cells was non-permissive for long-term growth, as shown by reduced colony formation compared with cells expressing either control vector or E198A mutant MMP-8. In long-term culture of transfected MDA-MB-231 cells, expression of WT but not E198A mutant MMP-8 was lost, with IL-6 and IL-8 levels returning to base line. Rare clonal isolates of MDA-MB-231 cells expressing WT MMP-8 were generated, and these showed constitutively high levels of IL-6 and IL-8, although production of the interleukins was no longer dependent upon MMP-8 activity. These studies support a causal connection between MMP-8 activity and the IL-6/IL-8 network, with an acute response to MMP-8 involving induction of the proinflammatory mediators, which may in part serve to compensate for the deleterious effects of MMP-8 on breast cancer cell growth. This axis may be relevant to the recognized ability of MMP-8 to orchestrate the innate immune system in inflammation in vivo.

scholarly journals R-sulforaphane modulates the expression profile of AhR, ERα, Nrf2, NQO1, and GSTP in human breast cell lines

2020 ◽  
Author(s):  
Barbara Licznerska ◽  
Hanna Szaefer ◽  
Violetta Krajka-Kuźniak
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Breast Cancer Cells ◽  
Gene Transcript ◽  
Mcf7 Cells ◽  
Protein Levels ◽  
Breast Cell Lines ◽  
Breast Cells ◽  
Ahr Gene

Abstract Our previous study showed remarkable differences in the effect of R-sulforaphane (R-SFN) on the expression of CYPs 19, 1A1, 1A2, and 1B1 in ER(+) MCF7, ER( −) MDA-MB-231, and non-tumorigenic immortalized MCF10A (8). This study aimed to evaluate the effect of R-SFN on phase II enzymes induction and expression of AhR, Nrf2, and ERα in the same breast cell lines. The results showed increased expression of GSTP as a result of treatment with R-SFN in breast cancer cells. An increased NQO1 transcript and protein levels were found in all breast cells, with the most significant increase in MCF7 cells. Similarly, the enhancement of Nrf2 expression was noticed in all tested cells. AhR gene transcript and protein were decreased in MCF7 cells. In MDA-MB-231, increased AhR mRNA was not confirmed at the protein level. No differences were found in the expression of ERα. Overall, the results of the present study extended our earlier suggestions on the possible interference of R-SFN with estrogens homeostasis in breast cancer cells differing in ERα status, as well as in non-tumorigenic immortalized breast epithelial cells. While some of R-SFN effects might be beneficial and useful in breast cancer prevention, the others, particularly GSTP induction, may lead to adverse effects.

Brave New Hope for Breast Cancer Aminopyrazole derivates between rational design and clinical efficacy

2017 ◽  
Vol 68 (4) ◽  
pp. 754-757 ◽  
Author(s):  
George Mihai Nitulescu ◽  
George Iancu ◽  
Georgiana Nitulescu ◽  
Raluca Claudia Iancu ◽  
Camelia Bogdanici ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Biology ◽  
Rational Design ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Proliferative Effect

Breast cancer research is a priority nowadays because of the high burden the disease represents for health systems worldwide. New agents are intensively researched to overcome breast cancer biology. Our aminopyrazole derivatives showed promising results when tested in vitro on breast cancer cell lines, by inhibiting protein kinase pathways. Anti-proliferative effect of pyrazole compounds on different breast cancer cell lines was heterogeneous. Further research is necessary to design the optimal structure in terms of high antitumor efficacy and good safety profile. Ophthalmologist control is very important for patients with breast cancer because treatment with some drugs reported side ocular effects: cataract, maculopathy (crystals or drusen or yellowish spots), retinal hemorrhages or dry.

scholarly journals Immunohistochemical Expression of RARα, RARβ, and Cx43 in Breast Tumor Cell Lines After Treatment With Lycopene and Correlation With RT-QPCR

2007 ◽  
Vol 55 (9) ◽  
pp. 877-883 ◽  
Author(s):  
Nasseéra Chalabi ◽  
Laetitia Delort ◽  
Samir Satih ◽  
Pierre Déchelotte ◽  
Yves-Jean Bignon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Connexin 43 ◽  
Breast Cancer Cell Lines ◽  
Pcr Analysis ◽  
Cx43 Expression ◽  
Real Time Quantitative Pcr ◽  
Protein Levels ◽  
Gap Junction Communication ◽  
Mcf 7

Lycopene, the major carotenoid found in tomatoes, is a potent antioxidant associated with the prevention of degenerative diseases such as breast cancer. This effect could be due to the interaction between lycopene and retinoic acid receptors as well as the stimulation of gap junction communication and synthesis of connexin 43. The expression of the RARα, RARβ, and Cx43 proteins was analyzed using immunohistochemistry in two breast cancer cell lines, MCF-7 and MDA-MB-231, and in a fibrocystic dystrophy cell line, MCF-10a, after a 48-hr exposure to 10 μM lycopene. A real-time quantitative PCR analysis was then performed to measure mRNA expression. RARα and Cx43 expression were increased at both mRNA and protein levels in two breast cell lines.

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