scholarly journals Interleukin-32θ Triggers Cellular Senescence and Reduces Sensitivity to Doxorubicin-Mediated Cytotoxicity in MDA-MB-231 Cells

2021 ◽  
Vol 22 (9) ◽  
pp. 4974
Author(s):  
Thu-Huyen Pham ◽  
Hyo-Min Park ◽  
Jinju Kim ◽  
Jin-Tae Hong ◽  
Do-Young Yoon
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Metastatic Breast ◽  
Mitotic Division ◽  
Cancer Cell Growth ◽  
Antiproliferative Effects ◽  
Cycle Arrest ◽  
Permanent Cell ◽  
In Cells

The recently discovered interleukin (IL)- 32 isoform IL-32θ exerts anti-metastatic effects in the breast tumor microenvironment. However, the involvement of IL-32θ in breast cancer cell proliferation is not yet fully understood; therefore, the current study aimed to determine how IL-32θ affects cancer cell growth and evaluated the responses of IL-32θ-expressing cells to other cancer therapy. We compared the functions of IL-32θ in triple-negative breast cancer MDA-MB-231 cells that stably express IL-32θ, with MDA-MB-231 cells transfected with a mock vector. Slower growth was observed in cells expressing IL-32θ than in control cells, and changes were noted in nuclear morphology, mitotic division, and nucleolar size between the two groups of cells. Interleukin-32θ significantly reduced the colony-forming ability of MDA-MB-231 cells and induced permanent cell cycle arrest at the G1 phase. Long-term IL-32θ accumulation triggered permanent senescence and chromosomal instability in MDA-MB-231 cells. Genotoxic drug doxorubicin (DR) reduced the viability of MDA-MB-231 cells not expressing IL-32θ more than in cells expressing IL-32θ. Overall, these findings suggest that IL-32θ exerts antiproliferative effects in breast cancer cells and initiates senescence, which may cause DR resistance. Therefore, targeting IL-32θ in combination with DR treatment may not be suitable for treating metastatic breast cancer.

Reversal of the glycolytic phenotype by dichloroacetate inhibits metastatic breast cancer cell growth in vitro and in vivo

2009 ◽  
Vol 120 (1) ◽  
pp. 253-260 ◽  
Author(s):  
Ramon C. Sun ◽  
Mitali Fadia ◽  
Jane E. Dahlstrom ◽  
Christopher R. Parish ◽  
Philip G. Board ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cell Growth ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Metastatic Breast ◽  
Cancer Cell Growth ◽  
Breast Cancer Cell Growth

scholarly journals ICT1 knockdown inhibits breast cancer cell growth via induction of cell cycle arrest and apoptosis

2017 ◽  
Vol 39 (4) ◽  
pp. 1037-1045 ◽  
Author(s):  
Chen Wang ◽  
Chenlu Liang ◽  
Weiliang Feng ◽  
Xianghou Xia ◽  
Feng Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Growth ◽  
Cell Cycle Arrest ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Growth ◽  
Breast Cancer Cell Growth ◽  
Cycle Arrest

scholarly journals BTG1 inhibits breast cancer cell growth through induction of cell cycle arrest and apoptosis

2013 ◽  
Vol 30 (5) ◽  
pp. 2137-2144 ◽  
Author(s):  
RAN ZHU ◽  
SHI-TAO ZOU ◽  
JIAN-MEI WAN ◽  
WEI LI ◽  
XIN-LI LI ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Growth ◽  
Cell Cycle Arrest ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Growth ◽  
Breast Cancer Cell Growth ◽  
Cycle Arrest

scholarly journals Estrogen-Induced Cell Cycle Arrest and Apoptosis as an Unexpected Outcome of Aromatase Inhibitor-Resistance in ER+ Breast Cancer

2021 ◽  
Author(s):  
Hitomi Mori ◽  
Kohei Saeki ◽  
Gregory Chang ◽  
Pei-Yin Hsu ◽  
Jinhui Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Aromatase Inhibitor ◽  
Single Cell ◽  
Cell Cycle Arrest ◽  
Tumor Regression ◽  
Metastatic Breast ◽  
Sequencing Analysis ◽  
Cycle Arrest

Abstract Background: Estrogen is known to promotes hormone-dependent breast cancer through activation of estrogen receptor (ER)-α encoded by ESR1. However, several clinical trials reported the unexpected therapeutic benefit of E2 for aromatase inhibitor (AI)-resistant cases of ER+ breast cancer. Considering potential impact of such clinical observation, we decided to determine the mechanisms of estrogen-induced tumor regression. Methods: A unique estrogen-inhibitory patient-derived xenograft (PDX) tumor, GS3, was established from an AI resistant ER+/HER2– brain metastatic breast cancer. In vivo estrogen suppression was confirmed through experiments by implanting 17β-estradiol (E2) pellets in mice carrying GS3, and then the single-cell analysis was performed using GS3 tumors. In vitro E2 suppression analysis was carried out using organoids from GS3.Results: The E2-induced suppression of GS3 involves ERα, which was wild-type and not amplified. Single cell RNA sequencing analysis of this PDX has revealed that E2 treatment (for 1 week) induces cell cycle arrest in both ESR1+ cells and ESR1– cells, demonstrating the unexpected influence of estrogen on ESR1– cells in ER+ breast cancer. E2 upregulated the expression of estrogen-regulated genes, including a tumor suppressor gene, IL24, and lower levels of IL24 were linked to estrogen independence, after three rounds of intermittent E2 treatment. IL24+ cells included more G1 phase cells of cell cycle compared to IL24– cells. Hallmark apoptosis gene sets were upregulated and the hallmark G2M checkpoint gene set was downregulated in IL24+ cells after E2 treatment. The number of apoptotic cells was significantly increased after long term (for 4 weeks) E2 treatment. Western blotting analysis demonstrated that long term E2 treatment induced expression of apoptosis-associated protein cleaved-PARP and reduction of the pro-survival protein Bcl-xl level.Conclusions: There is the need of markers for patients who can benefit from E2 treatment after AI resistance, and measurements of ER and PR expression are not enough. Analysis of GS3 PDX has revealed that estrogen induces cell cycle arrest and apoptosis. Our study has revealed the cross-talk between ESR1+ and ESR1– cells as well as potential roles of IL24 in estrogen-suppressive tumors.

18. Reversal of the glycolytic phenotype by dichloroacetate inhibits metastatic breast cancer cell growth in vitro and in vivo

Pathology ◽  
2010 ◽  
Vol 42 ◽  
pp. S87
Author(s):  
Ramon C. Sun ◽  
Mitali Fadia ◽  
Jane E. Dahlstrom ◽  
Christopher R. Parish ◽  
Philip G. Board ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cell Growth ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Metastatic Breast ◽  
Cancer Cell Growth ◽  
Breast Cancer Cell Growth

scholarly journals The new biology of estrogen-induced apoptosis applied to treat and prevent breast cancer

2014 ◽  
Vol 22 (1) ◽  
pp. R1-R31 ◽  
Author(s):  
V Craig Jordan
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Metastatic Breast ◽  
Cell Populations ◽  
Estrogen Deprivation ◽  
New Biology ◽  
Induced Apoptosis ◽  
Selection Of

The successful use of high-dose synthetic estrogens to treat postmenopausal metastatic breast cancer is the first effective ‘chemical therapy’ proven in clinical trial to treat any cancer. This review documents the clinical use of estrogen for breast cancer treatment or estrogen replacement therapy (ERT) in postmenopausal hysterectomized women, which can either result in breast cancer cell growth or breast cancer regression. This has remained a paradox since the 1950s until the discovery of the new biology of estrogen-induced apoptosis at the end of the 20th century. The key to triggering apoptosis with estrogen is the selection of breast cancer cell populations that are resistant to long-term estrogen deprivation. However, estrogen-independent growth occurs through trial and error. At the cellular level, estrogen-induced apoptosis is dependent upon the presence of the estrogen receptor (ER), which can be blocked by nonsteroidal or steroidal antiestrogens. The shape of an estrogenic ligand programs the conformation of the ER complex, which, in turn, can modulate estrogen-induced apoptosis: class I planar estrogens (e.g., estradiol) trigger apoptosis after 24 h, whereas class II angular estrogens (e.g., bisphenol triphenylethylene) delay the process until after 72 h. This contrasts with paclitaxel, which causes G2 blockade with immediate apoptosis. The process is complete within 24 h. Estrogen-induced apoptosis is modulated by glucocorticoids and cSrc inhibitors, but the target mechanism for estrogen action is genomic and not through a nongenomic pathway. The process is stepwise through the creation of endoplasmic reticulum stress and inflammatory responses, which then initiate an unfolded protein response. This, in turn, initiates apoptosis through the intrinsic pathway (mitochondrial) with the subsequent recruitment of the extrinsic pathway (death receptor) to complete the process. The symmetry of the clinical and laboratory studies now permits the creation of rules for the future clinical application of ERT or phytoestrogen supplements: a 5-year gap is necessary after menopause to permit the selection of estrogen-deprived breast cancer cell populations to cause them to become vulnerable to apoptotic cell death. Earlier treatment with estrogen around menopause encourages growth of ER-positive tumor cells, as the cells are still dependent on estrogen to maintain replication within the expanding population. An awareness of the evidence that the molecular events associated with estrogen-induced apoptosis can be orchestrated in the laboratory in estrogen-deprived breast cancers now supports the clinical findings regarding the treatment of metastatic breast cancer following estrogen deprivation, decreases in mortality following long-term antihormonal adjuvant therapy, and the results of treatment with ERT and ERT plus progestin in the Women's Health Initiative for women over the age of 60. Principles have emerged for understanding and applying physiological estrogen therapy appropriately by targeting the correct patient populations.

scholarly journals Osteoblast-Derived Paracrine and Juxtacrine Signals Protect Disseminated Breast Cancer Cells from Stress

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1366
Author(s):  
Russell Hughes ◽  
Xinyue Chen ◽  
Natasha Cowley ◽  
Penelope D. Ottewell ◽  
Rhoda J. Hawkins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Survival ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Accessory Cell ◽  
Cancer Cell Survival

Metastatic breast cancer in bone is incurable and there is an urgent need to develop new therapeutic approaches to improve survival. Key to this is understanding the mechanisms governing cancer cell survival and growth in bone, which involves interplay between malignant and accessory cell types. Here, we performed a cellular and molecular comparison of the bone microenvironment in mouse models representing either metastatic indolence or growth, to identify mechanisms regulating cancer cell survival and fate. In vivo, we show that regardless of their fate, breast cancer cells in bone occupy niches rich in osteoblastic cells. As the number of osteoblasts in bone declines, so does the ability to sustain large numbers of breast cancer cells and support metastatic outgrowth. In vitro, osteoblasts protected breast cancer cells from death induced by cell stress and signaling via gap junctions was found to provide important juxtacrine protective mechanisms between osteoblasts and both MDA-MB-231 (TNBC) and MCF7 (ER+) breast cancer cells. Combined with mathematical modelling, these findings indicate that the fate of DTCs is not controlled through the association with specific vessel subtypes. Instead, numbers of osteoblasts dictate availability of protective niches which breast cancer cells can colonize prior to stimulation of metastatic outgrowth.

scholarly journals MiR-205 Dysregulations in Breast Cancer: The Complexity and Opportunities

2019 ◽  
Vol 5 (4) ◽  
pp. 53 ◽  
Author(s):  
Xiao ◽  
Humphries ◽  
Yang ◽  
Wang
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Target Gene ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Breast ◽  
Therapy Resistance ◽  
Cancer Cell Proliferation ◽  
Mesenchymal Transition

MicroRNAs (miRNAs) are endogenous non-coding small RNAs that downregulate target gene expression by imperfect base-pairing with the 3′ untranslated regions (3′UTRs) of target gene mRNAs. MiRNAs play important roles in regulating cancer cell proliferation, stemness maintenance, tumorigenesis, cancer metastasis, and cancer therapeutic resistance. While studies have shown that dysregulation of miRNA-205-5p (miR-205) expression is controversial in different types of human cancers, it is generally observed that miR-205-5p expression level is downregulated in breast cancer and that miR-205-5p exhibits a tumor suppressive function in breast cancer. This review focuses on the role of miR-205-5p dysregulation in different subtypes of breast cancer, with discussions on the effects of miR-205-5p on breast cancer cell proliferation, epithelial–mesenchymal transition (EMT), metastasis, stemness and therapy-resistance, as well as genetic and epigenetic mechanisms that regulate miR-205-5p expression in breast cancer. In addition, the potential diagnostic and therapeutic value of miR-205-5p in breast cancer is also discussed. A comprehensive list of validated miR-205-5p direct targets is presented. It is concluded that miR-205-5p is an important tumor suppressive miRNA capable of inhibiting the growth and metastasis of human breast cancer, especially triple negative breast cancer. MiR-205-5p might be both a potential diagnostic biomarker and a therapeutic target for metastatic breast cancer.

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