scholarly journals Baicalin Enhances Chemosensitivity to Doxorubicin in Breast Cancer Cells via Upregulation of Oxidative Stress-Mediated Mitochondria-Dependent Apoptosis

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1506
Author(s):  
Mei-Yi Lin ◽  
Wan-Ting Cheng ◽  
Hui-Ching Cheng ◽  
Wan-Ching Chou ◽  
Hsiu-I Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Critical Issue ◽  
Breast Cancers ◽  
Apoptosis Pathway ◽  
Scutellaria Baicalensis Georgi ◽  
Intrinsic Apoptosis Pathway ◽  
Intracellular Ros ◽  
Cellular Apoptosis

Doxorubicin (Dox) is an effective anthracycline anticancer drug. However, recent studies have revealed that Dox resistance is a highly critical issue, and a significant reason for treatment failure. Baicalin is a flavonoid component in the roots of Scutellaria baicalensis Georgi; however, whether baicalin can increase chemosensitivity in breast cancers is still unclear. In this study, we found that cellular apoptosis occurs when excessive intracellular ROS is generated, triggered by the dual intervention of baicalin and doxorubicin, which increases intracellular calcium [Ca2+]i concentrations. Increased [Ca2+]i concentrations decrease the mitochondrial membrane potential (△Ψm), thereby causing cellular apoptosis. Pretreatment with NAC (ROS inhibitor) or BATBA (Ca2+ chelator) reduces baicalin-induced chemosensitivity. The findings of this study demonstrate that the effect of baicalin on Dox treatment could enhance cytotoxicity toward breast cancer cells via the ROS/[Ca2+]i-mediated intrinsic apoptosis pathway—thus potentially lessening the required dosage of doxorubicin, and further exploring associated mechanisms in combined treatments for breast cancer clinical interventions in the future.

scholarly journals Upregulation of SHMT2 Promotes Tumor Growth and Poor Prognosis of Breast Cancer through Activating VEGF and MAPK Signaling Pathway

2021 ◽  
Author(s):  
Shuang-Yan Xie ◽  
Dingbo Shi ◽  
Fei Lin ◽  
Xiao-Yu Cheng ◽  
Tong-chao Cheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Breast Cancer Cells ◽  
Mapk Signaling ◽  
Nucleotide Metabolism ◽  
Breast Cancers ◽  
Apoptosis Pathway

Abstract Background: Serine hydroxymethyltransferase 2 (SHMT2) is a key enzyme in Serine/glycine metabolism. SHMT2 is very important for tumor cell growth and proliferation as well as metabolism. Here, we investigated the regulatory effects of SHMT2 on breast cancers growth and identified the underlying mechanisms of functions.Methods: We detected the expression of SHMT2 in breast cancer cells and tissues by immunohistochemistry and Western blotting.We investigated the functional and molecular mechanisms by which SHMT2 downregulation or overexpression regulates the growth and apoptosis of breast cancer cells in vivo and in vitro. Results: We found SHMT2 was highly expressed in BRCA cell lines and tumor tissues. Strong SHMT2 expression showed a positive correlation with the poor prognoses of patients with breast cancers. SHMT2 knockdown by shRNA significantly inhibited cell growth and induced apoptosis in vitro, and whereas SHMT2 overexpression promoted tumor growthin in subcutaneous xenograft model. RNA-seq revealed that high expression of SHMT2 not only promoted serine metabolism, nucleotide metabolism, oxidative phosphorylation and proteasome independent degradation pathways. It also activated the cell survival signaling pathway and antagonized the apoptosis pathway. The observed molecular regulation of cell growth was accompanied by the activited of the MAPK, VEGF pathways and suppressed of the mitochondrial mediated apoptosis pathway that was mediated by the SHMT2 up-regulation. Conclusions: These results indicate that SHMT2 plays a critical role in regulating breast cancers growth and could serve as a therapeutic target for breast cancer therapy.

scholarly journals Transcriptional coregualtor NUPR1 maintains tamoxifen resistance in breast cancer cells

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Lingling Wang ◽  
Jiashen Sun ◽  
Yueyuan Yin ◽  
Yanan Sun ◽  
Jinyi Ma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Critical Role ◽  
Endocrine Resistance ◽  
Autophagic Flux ◽  
Physical Interaction ◽  
Premature Senescence ◽  
Breast Cancers ◽  
Transcriptional Coregulator

AbstractTo support cellular homeostasis and mitigate chemotherapeutic stress, cancer cells must gain a series of adaptive intracellular processes. Here we identify that NUPR1, a tamoxifen (Tam)-induced transcriptional coregulator, is necessary for the maintenance of Tam resistance through physical interaction with ESR1 in breast cancers. Mechanistically, NUPR1 binds to the promoter regions of several genes involved in autophagy process and drug resistance such as BECN1, GREB1, RAB31, PGR, CYP1B1, and regulates their transcription. In Tam-resistant ESR1 breast cancer cells, NUPR1 depletion results in premature senescence in vitro and tumor suppression in vivo. Moreover, enforced-autophagic flux augments cytoplasmic vacuolization in NUPR1-depleted Tam resistant cells, which facilitates the transition from autophagic survival to premature senescence. Collectively, these findings suggest a critical role for NUPR1 as a transcriptional coregulator in enabling endocrine persistence of breast cancers, thus providing a vulnerable diagnostic and/or therapeutic target for endocrine resistance.

scholarly journals Transcriptome profiles of stem-like cells from primary breast cancers allow identification of ITGA7 as a predictive marker of chemotherapy response

2021 ◽  
Author(s):  
Noha Gwili ◽  
Stacey J. Jones ◽  
Waleed Al Amri ◽  
Ian M. Carr ◽  
Sarah Harris ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Predictive Marker ◽  
Therapy Resistance ◽  
Differentially Expressed ◽  
Molecular Profile ◽  
Chemotherapy Response ◽  
Breast Cancers

Abstract Background Breast cancer stem cells (BCSCs) are drivers of therapy-resistance, therefore are responsible for poor survival. Molecular signatures of BCSCs from primary cancers remain undefined. Here, we identify the consistent transcriptome of primary BCSCs shared across breast cancer subtypes, and we examine the clinical relevance of ITGA7, one of the genes differentially expressed in BCSCs. Methods Primary BCSCs were assessed using immunohistochemistry and fluorescently labelled using Aldefluor (n = 17). Transcriptomes of fluorescently sorted BCSCs and matched non-stem cancer cells were determined using RNA-seq (n = 6). ITGA7 expression was examined in breast cancers using immunohistochemistry (n = 305), and its functional role was tested using siRNA in breast cancer cells. Results Proportions of BCSCs varied from 0 to 9.4%. 38 genes were significantly differentially expressed in BCSCs; genes were enriched for functions in vessel morphogenesis, motility, and metabolism. ITGA7 was found to be significantly downregulated in BCSCs, and low expression significantly correlated with reduced survival in patients treated with chemotherapy, and with chemoresistance in breast cancer cells in vitro. Conclusions This study is the first to define the molecular profile of BCSCs from a range of primary breast cancers. ITGA7 acts as a predictive marker for chemotherapy response, in accordance with its downregulation in BCSCs.

scholarly journals Spot 14: A Marker of Aggressive Breast Cancer and a Potential Therapeutic Target

Endocrinology ◽  
2006 ◽  
Vol 147 (9) ◽  
pp. 4048-4055 ◽  
Author(s):  
William B. Kinlaw ◽  
Jennifer L. Quinn ◽  
Wendy A. Wells ◽  
Christopher Roser-Jones ◽  
Joel T. Moncur
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Therapeutic Target ◽  
Milk Fat ◽  
Breast Cancer Cells ◽  
De Novo ◽  
Lipid Synthesis ◽  
Breast Cancers ◽  
Spot 14 ◽  
Aggressive Breast Cancer

Spot 14 (S14) is a nuclear protein that communicates the status of dietary fuels and fuel-related hormones to genes required for long-chain fatty acid synthesis. In mammary gland, S14 is important for both epithelial proliferation and milk fat production. The S14 gene is amplified in some breast cancers and is strongly expressed in most. High expression of S14 in primary invasive breast cancer is conspicuously predictive of recurrence. S14 mediates the induction of lipogenesis by progestin in breast cancer cells and accelerates their growth. Conversely, S14 knockdown impairs de novo lipid synthesis and causes apoptosis. We found that breast cancer cells do not express lipoprotein lipase (LPL) and hypothesize that they do not have access to circulating lipids unless the local environment supplies it. This may explain why primary breast cancers with low S14 do not survive transit from the LPL-rich mammary fat pad to areas devoid of LPL, such as lymph nodes, and thus do not appear as distant metastases. Thus, S14 is a marker for aggressive breast cancer and a potential target as well. Future effort will center on validation of S14 as a therapeutic target and producing antagonists of its action.

Antineoplastic Efectiveness of Silver Nanoparticles Synthesized from Onopordum Acanthium L. extract (AgNPs-OAL) toward MDA-MB231 Breast Cancer Cells

2021 ◽  
Author(s):  
Romina Delalat ◽  
Seyed Ataollah Sadat Shandiz ◽  
Bahareh Pakpour
Keyword(s):  
Breast Cancer ◽  
Silver Nanoparticles ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Annexin V ◽  
Spherical Shape ◽  
Hek293 Cells ◽  
Apoptosis Pathway ◽  
Onopordum Acanthium

Abstract The present research was done to investigate the anticancer properties of silver nanoparticles (AgNPs) fabricated using bioactive extract of Onopordum acanthium L. (AgNPs-OAL) against breast cancer cell MDA_MB231 in vitro. The determination studies of AgNPs-OAL were confirmed by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) analysis. Interestingly, FESEM image observed the spherical shape of AgNPs-OAL with the range of 1–100 nm. As AgNP-OAL exhibited significant cytotoxicity properties on breast cancer MDA_MB231 cells with IC50 values of 66.04 μg/mL, while lowing toxicity toward normal human embryonic kidney 293 (HEK293) cells with IC50 values of 101.04 μg/mL was evaluated. Further, up-regulation of apoptotic Bax and CAD genes expressions were confirmed by quantitative real-time reverse transcription-PCR (qRT-PCR) technique results. Moreover, enhanced cell cycle population (sub-G1), annexin V/PI staining, acridine orange and ethidium bromide (AO/EB) staining, Hoescht 33258 dye, and generation of reactive oxygen species (ROS) observed in AgNP-OAL-treated MDA_MB231 cancer cells. The green-synthesized AgNP-OAL has promising anticancer efficiency that can trigger apoptosis pathway in the MDA_MB231 breast cancer cells.

scholarly journals Selective Effects of Thioridazine on Self-Renewal of Basal-Like Breast Cancer Cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Matthew Tegowski ◽  
Cheng Fan ◽  
Albert S. Baldwin
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Cell Types ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Self Renewal ◽  
Basal Like Breast Cancer

AbstractSeveral recent publications demonstrated that DRD2-targeting antipsychotics such as thioridazine induce proliferation arrest and apoptosis in diverse cancer cell types including those derived from brain, lung, colon, and breast. While most studies show that 10–20 µM thioridazine leads to reduced proliferation or increased apoptosis, here we show that lower doses of thioridazine (1–2 µM) target the self-renewal of basal-like breast cancer cells, but not breast cancer cells of other subtypes. We also show that all breast cancer cell lines tested express DRD2 mRNA and protein, regardless of thioridazine sensitivity. Further, DRD2 stimulation with quinpirole, a DRD2 agonist, promotes self-renewal, even in cell lines in which thioridazine does not inhibit self-renewal. This suggests that DRD2 is capable of promoting self-renewal in these cell lines, but that it is not active. Further, we show that dopamine can be detected in human and mouse breast tumor samples. This observation suggests that dopamine receptors may be activated in breast cancers, and is the first time to our knowledge that dopamine has been directly detected in human breast tumors, which could inform future investigation into DRD2 as a therapeutic target for breast cancer.

scholarly journals Review of: Tamoxifen and TRAIL synergistically induce apoptosis in breast cancer cells

2008 ◽  
Vol 11 (2) ◽  
Author(s):  
Alison J. Butt
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Single Agent ◽  
Xenograft Model ◽  
Estrogen Receptor Α ◽  
Tumor Xenograft ◽  
Breast Cancers ◽  
Induced Apoptosis

Citation of original article:C. Lagadec, E. Adriaenssens, R. A. Toillon, V. Chopin, R. Romon, F. Van Coppenolle, H. Hondermarck, X. Le Bourhis. Oncogene advance online publication, 3 September 2007; doi:10.1038/sj.onc.1210749.Abstract of the original article:Tamoxifen (TAM), is widely used as a single agent in adjuvant treatment of breast cancer. Here, we investigated the effects of TAM in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in estrogen receptor-α (ER-α)-positive and -negative breast cancer cells. We showed that cotreatment with TAM and TRAIL synergistically induced apoptosis regardless of ER-α status. By contrast, cotreatment did not affect the viability of normal breast epithelial cells. Cotreatment with TAM and TRAIL in breast cancer cells decreased the levels of antiapoptotic proteins including FLIPs and Bcl-2, and enhanced the levels of proapoptotic proteins such as FADD, caspase 8, tBid, Bax and caspase 9. Furthermore, cotreatment-induced apoptosis was efficiently reduced by FADD- or Bid-siRNA, indicating the implication of both extrinsic and intrinsic pathways in synergistic apoptosis induction. Importantly, cotreatment totally arrested tumor growth in an ER-α-negative MDA-MB-231 tumor xenograft model. The abrogation of tumor growth correlated with enhanced apoptosis in tumor tissues. Our findings raise the possibility to use TAM in combination with TRAIL for breast cancers, regardless of ER-α status.

scholarly journals The Role of Aryl Hydrocarbon Receptor and Crosstalk with Estrogen Receptor in Response of Breast Cancer Cells to the Novel Antitumor Agents Benzothiazoles and Aminoflavone

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Mariana A. Callero ◽  
Andrea I. Loaiza-Pérez
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Aryl Hydrocarbon Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Antitumor Agents ◽  
Breast Cancers ◽  
Nude Mouse Model ◽  
Aryl Hydrocarbon ◽  
Mcf 7

Many estrogen-receptor- (ER-) expressing breast cancers become refractory to ER-based therapies. New antitumor drugs like aminoflavone (AF) and benzothiazoles (Bzs) have been developed and have exquisite antitumor activity in ER+MCF-7 and T47D cells and in a MCF-7 nude mouse model. ER(−) breast cancer cells like MDA-MB-231 are less susceptible. We previously found in MCF-7 cells that these drugs activate the aryl hydrocarbon receptor (AhR) via translocation to the nucleus, induction of AhR-specific DNA binding activity, and expression of CYP1A1, whose transcription is controlled by the AhR-ARNT transcription factor. CYP1A1 metabolizes AF and Bz to a species which directly or after further metabolism damages DNA. In contrast an AhR-deficient variant of MCF-7 or cells with predominantly nuclear AhR expression, such as MDA-MB 231, are resistant. Thus, these drugs, unlike other neoplastic agents, require AhR-mediated signaling to cause DNA damage. This is a new treatment strategy for breast cancers with intact AhR signaling.

scholarly journals Identification of hub genes associated with RNAi-induced silencing of XIAP through targeted proteomics approach in MCF7 cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mehdi Agha Gholizadeh ◽  
Fatemeh T. Shamsabadi ◽  
Ahad Yamchi ◽  
Masoud Golalipour ◽  
Gagan Deep Jhingan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Specific Antigen ◽  
Mapk Signaling ◽  
2D Electrophoresis ◽  
Mcf7 Cells ◽  
Apoptosis Pathway ◽  
Apoptosis Protein ◽  
Mcf 7

Abstract Background The X-linked inhibitor of apoptosis protein (XIAP) is the most potent caspase inhibitor of the IAP family in apoptosis pathway. This study aims to identify the molecular targets of XIAP in human breast cancer cells exposed to XIAP siRNA by proteomics screening. The expression of XIAP was reduced in MCF-7 breast cancer cells by siRNA. Cell viability and the mRNA expression level of this gene were evaluated by MTS and quantitative real-time PCR procedures, respectively. Subsequently, the XIAP protein level was visualized by Western blotting and analyzed by two-dimensional (2D) electrophoresis and LC–ESI–MS/MS. Results Following XIAP silencing, cell proliferation was reduced in XIAP siRNA transfected cells. The mRNA transcription and protein expression of XIAP were decreased in cells exposed to XIAP siRNA than si-NEG. We identified 30 proteins that were regulated by XIAP, of which 27 down-regulated and 3 up-regulated. The most down-regulated proteins belonged to the Heat Shock Proteins family. They participate in cancer related processes including apoptosis and MAPK signaling pathway. Reduced expression of HSP90B1 was associated with apoptosis induction by androgen receptor and prostate specific antigen. Suppression of XIAP resulted in the enhancement of GDIB, ENO1, and CH60 proteins expression. The network analysis of XIAP-regulated proteins identified HSPA8, HSP90AA1, ENO1, and HSPA9 as key nodes in terms of degree and betweenness centrality methods. Conclusions These results suggested that XIAP may have a number of biological functions in a diverse set of non-apoptotic signaling pathways and may provide an insight into the biomedical significance of XIAP over-expression in MCF-7 cells.

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