scholarly journals Chitosan nanoparticle-delivered siRNA reduces CXCR4 expression and sensitizes breast cancer cells to cisplatin

2017 ◽  
Vol 37 (3) ◽  
Author(s):  
Shaonan Yu ◽  
Yan Chen ◽  
Xuefeng Li ◽  
Zhongli Gao ◽  
Guifeng Liu
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cxcr4 Expression ◽  
Breast Cancers ◽  
Protein Levels ◽  
Chitosan Nanoparticle ◽  
Increased Sensitivity ◽  
Sirna Group ◽  
Mcf 7

Chemokine (C-X-C motif) receptor 4 (CXCR4) has been reported as a poor prognostic biomarker in human breast cancers, and has been suggested as a promising therapeutic target of breast cancer treatment. The present study aims to investigate the delivery efficiency of siRNA by chitosan into breast cancer cells, and then to examine the regulatory role by chitosan nanoparticle-delivered siRNA on CXCR4 expression and on the chemosensitivity of breast cancer cells. Our results demonstrated that the siRNA could be capsuled by chitosan into nanoparticles with a diameter of 80–110 nm, and with a zeta potential of 20–50 mV. The chitosan nanoparticle delivered siRNA efficiently into breast cancer MCF-7 cells significantly reduced the expression of CXCR4 in both mRNA and protein levels. Moreover, the reduced CXCR4 by chitosan nanoparticle-delivered siRNA was associated with increased sensitivity of breast cancer cells to cisplatin. Reduced growth and increased apoptosis of MCF-7 cells were observed in the CXCR4 siRNA group than in the control siRNA group. Taken together, our results present the treatment potential of chitosan nanoparticle-delivered siRNA targeting CXCR4 in breast cancers.

VITAMIN D DERIVATIVES IN COMBINATION WITH 9-cis RETINOIC ACID PROMOTE ACTIVE CELL DEATH IN BREAST CANCER CELLS

1995 ◽  
Vol 14 (3) ◽  
pp. 391-394 ◽  
Author(s):  
S Y James ◽  
A G Mackay ◽  
K W Colston
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Retinoic Acid ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
P53 Protein ◽  
Protein A ◽  
Therapeutic Implications ◽  
Protein Levels ◽  
Mcf 7

ABSTRACT The effects of the novel vitamin D analogue, EB1089 alone, or in combination with the retinoid, 9-cis retinoic acid (9-cis RA) on indices of apoptosis in MCF-7 breast cancer cells have been examined. EB1089 was capable of reducing bcl-2 protein, a suppressor of apoptosis, and increasing p53 protein levels in MCF-7 cell cultures following 96h treatment. In the presence of 9-cis RA, EB1089 acted to further enhance the down-regulation and up-regulation of bcl-2 and p53 respectively. Furthermore, EB1089 induces DNA fragmentation in MCF-7 cells, a key feature of apoptosis, alone and in combination with 9-cis RA in situ. The observation that EB1089 and 9-cis RA act in a cooperative manner to enhance induction of apoptosis in these cells may have therapeutic implications.

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 PAPOLA contributes to Cyclin D1 mRNA alternative polyadenylation and promotes breast cancer cells proliferation

2021 ◽  
pp. jcs.252304
Author(s):  
Chrysoula Komini ◽  
Irini Theohari ◽  
Andromachi Lambrianidou ◽  
Lydia Nakopoulou ◽  
Theoni Trangas
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Alternative Polyadenylation ◽  
Hek 293 ◽  
Protein Levels ◽  
293 Cells ◽  
Candidate Target ◽  
Mcf 7

Poly(A) polymerases add the poly(A) tail at the 3’ end of nearly all eukaryotic mRNA, are associated with proliferation and cancer. To elucidate the role of the most studied mammalian poly(A) polymerase α (PAPOLA) in cancer, we assessed its expression in 221 breast cancer samples and found it to correlate strongly with the aggressive triple-negative subtype. Silencing PAPOLA in MCF-7 and MDA-MB-231 breast cancer cells reduced proliferation and anchorage-independent growth by decreasing steady-state CCND1 mRNA and protein levels. Whereas the length of the CCND1 mRNA poly(A) tail was not affected, its 3' untranslated region (3'UTR) lengthened. Overexpressing PAPOLA caused CCND1 mRNA 3'UTR shortening with a concomitant increase in the corresponding transcript and protein, resulting in growth arrest in MCF-7 cells and DNA damage in HEK-293 cells, whereas in the P53 mutant MDA-MB-231 promoted proliferation.Our data suggest PAPOLA as a possible candidate target for the control of tumor growth, mostly relevant to triple-negative tumors, a group characterized by its overexpression and lacking alternative targeted therapies.

scholarly journals To explore immune synergistic function of Quercetin in inhibiting breast cancer cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dan Qiu ◽  
Xianxin Yan ◽  
Xinqin Xiao ◽  
Guijuan Zhang ◽  
Yanqiu Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Breast Cancer Cells ◽  
Γδ T Cells ◽  
Killing Effect ◽  
Protein Levels ◽  
Stat1 Signaling ◽  
Mcf 7

Abstract Background The precancerous disease of breast cancer is an inevitable stage in the tumorigenesis and development of breast neoplasms. Quercetin (Que) has shown great potential in breast cancer treatment by inhibiting cell proliferation and regulating T cell function. γδ T cells are a class of nontraditional T cells that have long attracted attention due to their potential in immunotherapy. In this study, we revealed the immunomodulatory function of Que through regulation of the JAK/STAT1 signaling pathway, which was followed by the synergistic killing of breast cancer cells. Methods In the experimental design, we first screened target genes with or without Que treatment, and we intersected the Que target with the disease target by functional enrichment analysis. Second, MCF-10A, MCF-10AT, MCF-7 and MDA-MB-231 breast cancer cell lines were treated with Que for 0 h, 24 h and 48 h. Then, we observed the expression of its subsets by coculturing Que and γδ T cells and coculturing Que and γδ T cells with breast tumor cells to investigate their synergistic killing effect on tumor cells. Finally, Western blotting was used to reveal the changes in proteins related to the JAK/STAT1 signaling pathway after Que treatment in MCF-10AT and MCF-7 cells for 48 h. Results The pathway affected by Que treatment was the JAK/STAT1 signaling pathway and was associated with precancerous breast cancer, as shown by network pharmacology analysis. Que induced apoptosis of MCF-10AT, MCF-7 and MDA-MB-231 cells in a time- and concentration-dependent manner (P < 0.05). Most importantly, Que promoted the differentiation of γδ T cells into the Vδ2 T cell subpopulation. The best ratio of effector cells to target cells (E/T) was 10:1, the killing percentages of γδ T cells against MCF-10A, MCF-10AT, MCF-7, and MDA-MB-231 were 61.44 ± 4.70, 55.52 ± 3.10, 53.94 ± 2.74, and 53.28 ± 1.73 (P = 0.114, P = 0.486, and P = 0.343, respectively), and the strongest killing effect on precancerous breast cancer cells and breast cancer cells was found when the Que concentration was 5 μM and the E/T ratio was 10:1 (64.94 ± 3.61, 64.96 ± 5.45, 55.59 ± 5.98, and 59.04 ± 5.67, respectively). In addition, our results showed that Que increased the protein levels of IFNγ-R, p-JAK2 and p-STAT1 while decreasing the protein levels of PD-L1 (P < 0.0001). Conclusions In conclusion, Que plays a synergistic role in killing breast cancer cells and promoting apoptosis by regulating the expression of IFNγ-R, p-JAK2, p-STAT1 and PD-L1 in the JAK/STAT1 signaling pathway and promoting the regulation of γδ T cells. Que may be a potential drug for the prevention of precancerous breast cancer and adjuvant treatment of breast cancer.

Pleiotrophin Secreted from Human Breast Cancer MCF-7-Ptn Cells Activates Stromal Fibroblasts, Induces Epithelial Island Formation, and Remodels the Microenvironment.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2568-2568 ◽  
Author(s):  
Masahiko Zuka ◽  
Yunchao Chang ◽  
Zhaoyi Wang ◽  
James R. Berenson ◽  
Thomas F. Deuel
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Breast Cancers ◽  
Human Breast ◽  
Nih3t3 Cells ◽  
Inappropriate Expression ◽  
Nih 3T3 ◽  
Mcf 7

Abstract Pleiotrophin (PTN, Ptn) is an 18 kD cytokine that is expressed in many human breast cancers and its gene is inappropriately expressed in cell lines derived from these breast cancers. To study the siginificance of inappropriate expression of Ptn in human breast cancer cells on surrounding stromal cells, we first compared nude mouse xenografts of MCF-7 and MCF-7-Ptn cells. MCF-7-Ptn cells lack the Receptor Protein Tyrosine Phosphatase (RPTP)b/z, the PTN receptor, and thus are not responsive to PTN through autocrine or paracrine stimulation. The MCF-7-Ptn cell xenografts grew rapidly whereas MCF-7 cells xenografts were barely detectable 6 weeks after injection. MCF-7-Ptn cells that were co-injected with equal numbers of NIH3T3 cells grew even more rapidly in the flanks of the nude mice. Surprisingly, the MCF-7-Ptn cell explants developed a morphological phenotype remarkably similar to that of the human invasive ductal carcinoma. We then co-cultured MCF-7 cells that express Ptn (MCF-7-Ptn cells) with NIH 3T3 cells. Secretion of PTN from MCF-7-Ptn cells induced formation of sharply defined clusters of MCF-7-Ptn cells, termed “epithelial islands”, that were surrounded by dense fibrous bands interspersed with NIH 3T3 cells that morphologically closely resemble carcinoma associated fibroblasts (CAFs). A striking increase in tropoelastin and expression of type IV procollagen mRNA was identified in NIH3T3 cells co-cultured with MCF-7-Ptn cells. Furthermore, different markers often resulting from stromal cell-carcinoma cell interactions in breast cancer, including protein kinase C (PKC)-d, and both human and murine matrix metalloproteinase (MMP) 9 were identified either in cells or in the culture media taken from MCF-7-Ptn/NIH3T3 cell co-cultures. The induction of these biochemical and morphological features in the co-cultures of MCF-7-Ptn and NIH3T3 cells was demonstrated to be Ptn expression dependent, PTN-secretion dependent, and NIH3T3 cell dependent. The data suggest that PTN secretion alone from human breast cancer cells with inappropriate expression of Ptn is sufficient to markedly remodel the microenvironment of the breast cancer cell and induce a morphological transition of the MCF-7-Ptn cells and NIH3T3 cells to patterns resembling breast carcinomas through activation of the PTN/RPTPb/z signaling pathway in NIH3T3 cells and reciprocal signaling between the carcinoma stromal cells and the PTN secreting breast cancer cells.

scholarly journals Effects of BET Inhibitor JQ1 and Interleukin-6 on Breast Cancer Cells

2021 ◽  
Author(s):  
Atefeh Sharif Hoseini ◽  
Masoud Heshmati ◽  
Amin Soltani ◽  
Hedayatollah Shirzad ◽  
Morteza Sedehi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Therapeutic Targets ◽  
Surface Expression ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Breast Cancers ◽  
Bet Inhibitors ◽  
Mcf 7

Abstract Bromodomain and extra-terminal (BET) proteins are recognized acetylated lysine of histone 4 and act as scaffolds to recruit many other proteins to promoters and at enhancers of active genes, especially at the super-enhancers of key genes, driving the transcription process and have been identified as potential therapeutic targets in breast cancer. However, the efficacy of BET inhibitors such as JQ1 in breast cancer therapy is impeded by IL-6 through an as yet defined mechanism. We investigated the interplay between IL-6 and JQ1 in MCF-7 and MDA-MB-231 human breast cancer cells. Here we demonstrate that the efficacy of JQ1 on the inhibition of cell growth and apoptosis was stronger in MDA-MB-231 cells than in MCF-7 cells. Further, MCF-7 cells, but not MDA-MB-231 cells, exhibited increased expression of CXCR4 following IL-6 treatment. JQ1 significantly reduced CXCR4 surface expression in both cell lines and diminished the effects of IL-6 pre-treatment on MCF-7 cells. While IL-6 suppressed the extension of breast cancer stem cells (BCSCs) in MCF-7 cells, JQ1 impeded its inhibitory effect. In addition, in MCF-7 cells JQ1 increased the number of senescent cells in a time-dependent manner. Analysis of gene expression indicated that JQ1 and IL-6 synergistically increase SNAIL expression and decrease c-MYC expression in MCF-7 cells. So, the BET proteins are promising, novel therapeutic targets in late-stage breast cancers.

scholarly journals Narciclasine Targets STAT3 via Distinct Mechanisms in Tamoxifen-Resistant Breast Cancer Cells

2021 ◽  
Author(s):  
Chao Lv ◽  
Yun Huang ◽  
Rui Huang ◽  
Qun Wang ◽  
Hongwei Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Sh2 Domain ◽  
Breast Cancers ◽  
Stat3 Phosphorylation ◽  
Er Positive ◽  
Tamoxifen Resistant ◽  
Mcf 7 ◽  
Positive Breast Cancer

Abstract Background: Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in multiple malignant tumors. Compared with regular estrogen receptor (ER)-positive breast cancers, the patients with tamoxifen-resistant breast cancers often exhibit higher level of STAT3 phosphorylation. Narciclasine (Nar) possesses strong inhibiting effects against a variety of cancer cells, however, the underlying antitumor target(s)/mechanism(s) remains barely understood. Methods: Targets prediction of narciclasine was performed by combining connectivity map (CMAP) and drug affinity responsive target stability (DARTS) strategy. Molecular and biochemical methods were used to elucidate the distinct mechanisms of narciclasine targeting STAT3. The narciclasine nano-delivery system was synthesized by thin film hydration method. Xenograft models were established to determine antitumor activity of narciclasine and its liposome in vivo.Results: In this study, we successfully identified the STAT3 was the direct target of Nar through the combination strategies of CMAP and DARTS. In ER-positive breast cancer cells, Nar could suppress phosphorylation, activation, dimerization, and nuclear translocation of STAT3 by directly binding with the STAT3 SH2 domain. Additionally, Nar could also specifically promote total STAT3 degradation via proteasome pathway and reduce the STAT3 protein stability in tamoxifen-resistant breast cancer cells (MCF-7/TR). This distinct mechanism of Nar targeting STAT3 was mainly attributed to the various levels of reactive oxygen species (ROS) in regular and tamoxifen-resistant ER-positive breast cancer cells. Meanwhile, Nar loaded nanoparticles could markedly decrease the protein levels of STAT3 in tumor sites, resulting in significant MCF-7/TR xenograft tumor regression without obvious toxicity. Conclusions: Our findings successfully highlight the STAT3 as the direct therapeutic target of Nar in ER-positive breast cancer cells, especially Nar leaded STAT3 degradation as a promising strategy for the tamoxifen-resistant breast cancer treatment.

scholarly journals Dihydroartemisinin-loaded Magnetic Nanoparticles for Enhanced Chemodynamic Therapy

2019 ◽  
Author(s):  
Shengdi Guo ◽  
Xianxian Yao ◽  
Qin Jiang ◽  
Kuang Wang ◽  
Yuanying Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Magnetic Nanoparticles ◽  
Cancer Cells ◽  
Therapeutic Effect ◽  
Breast Cancer Cells ◽  
Inhibitory Effect ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Ferrous Ions ◽  
Mcf 7

AbstractRecently, chemodynamic therapy (CDT) has represented a new approach for cancer treatment with low toxicity and side effects. Nonetheless, it has been a challenge to improve the therapeutic effect through increasing the amount of reactive oxygen species (ROS). Herein, we increased the amount of ROS agents in the Fenton-like reaction by loading dihydroartemisinin (DHA) which was an artemisinin (ART) derivative containing peroxide groups, into magnetic nanoparticles (MNP), thereby improving the therapeutic effect of CDT. Blank MNP were almost non-cytotoxic, whereas three MNP loading ART-based drugs, MNP-ART, MNP-DHA, and MNP-artesunate (MNP-AS), all showed significant killing effect on breast cancer cells (MCF-7 cells), in which MNP-DHA were the most potent. What’s more, the MNP-DHA showed high toxicity to drug-resistant breast cancer cells (MCF-7/ADR cells), demonstrating its ability to overcome multidrug resistance (MDR). The study revealed that MNP could produce ferrous ions under the acidic condition of tumor microenvironment, which catalyzed DHA to produce large amounts of ROS, leading to cell death. Further experiments also showed that the MNP-DHA had significant inhibitory effect on another two aggressive breast cancer cell lines (MDA-MB-231 and MDA-MB-453 cells), which indicated that the great potential of MNP-DHA for the treatment of intractable breast cancers.

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