scholarly journals Sialic acid-binding lectin-modified fructose-coated nanoparticles: a promising targeted therapeutic synthetic for breast cancers

2020 ◽  
Author(s):  
Lin He ◽  
Biyuan Zhang ◽  
Yuhua Song ◽  
Haiji Wang
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Tumor Cells ◽  
Cell Lines ◽  
Drug Effects ◽  
Multiple Drug ◽  
Her2 Overexpression ◽  
Breast Cancers ◽  
Coated Nanoparticles ◽  
Sialic Acid Binding

Abstract Background: Sialic acid-binding lectin (cSBL) specifically kills tumor cells rather than healthy cells. Glycopolymer-coated nanoparticles are selectively ingested by tumor cells because they can interact with the enriched carbohydrate receptors located on the surface of tumor cells. In this context, we synthesized cSBL-modified fructose-coated nanoparticles (LMFN) and cSBL-modified glucose-coated nanoparticles (LMGN) to investigate their anticancer activity in various molecular subtypes of breast cancer cell lines.Methods: The syntheses of fructose-coated nanoparticles and glucose-coated nanoparticles were based on the chemicals of 1,2:4,5-di-O-isopropylidene-β-d-fructopyranose and 1,2:4,5-di-O-isopropylidene-β-d-glucopyranose, respectively. The carbodiimide-based method was employed to synthesize LMFN and LMGN. The antitumor mechanism was explored by cell cycle analysis with flowcytometry and the antitumor activity was assessed by cytotoxicity assay and multiple drug effects analysis.Results: The cytotoxicity assay showed that LMFN had robust antitumor activity against all breast cancer phenotype cell lines whereas LMGN was rarely efficacious to against human epidermal growth factor receptor 2-positive/overexpression (HER2+/overexpression) breast cancer cells. The intrinsic reason for these findings was that the overexpression of fructose transporter, GLUT5, was observed in all breast cancer subtype cell lines but only a paucity of glucose transporter, GLUT1, was expressed in HER2+/overexpression breast cancer cell lines that dampened the uptake of LMGN to these cells. The cell cycle analysis indicated that the anticancer activity of LMFN was achieved by arresting cell cycle in S phase. The multiple drug effects analysis suggested the synergistic effect in the combinations of LMFN and tamoxifen to kill estrogen receptor+ breast cancer cells and LMFN and trastuzumab to kill HER2+/overexpressed breast cancer cells.Conclusion: Our work pinpoints that LMFN may be a new-onset selection for molecularly targeted therapy of breast cancers and paves the way for establishing its clinical application in the future.

scholarly journals Sialic acid-binding lectin-modified fructose-coated nanoparticles: a promising targeted therapeutic synthetic for breast cancers

2020 ◽  
Author(s):  
Lin He ◽  
Biyuan Zhang ◽  
Yuhua Song ◽  
Haiji Wang
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cell Lines ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines ◽  
Multiple Drug ◽  
Her2 Overexpression ◽  
Coated Nanoparticles

Abstract Background: Sialic acid-binding lectin (cSBL) specifically kills tumor cells rather than healthy cells. Glycopolymer-coated nanoparticles are selectively ingested by tumor cells because they can interact with the enriched carbohydrate receptors located on the surface of tumor cells. In this context, we synthesized cSBL-modified fructose-coated nanoparticles (LMFN) and cSBL-modified glucose-coated nanoparticles (LMGN) to investigate their anticancer activity in various molecular subtypes of breast cancer cell lines. Methods: The syntheses of fructose-coated nanoparticles and glucose-coated nanoparticles were based on the chemicals of 1,2:4,5-di- O -isopropylidene- β -d-fructopyranose and 1,2:4,5-di- O -isopropylidene- β -d-glucopyranose, respectively. The carbodiimide-based method was employed to synthesize LMFN and LMGN. The antitumor mechanism was explored by cell cycle analysis with flowcytometry and the antitumor activity was assessed by cytotoxicity assay and multiple drug effects analysis. Results: The cytotoxicity assay showed that LMFN had robust antitumor activity against all breast cancer phenotype cell lines whereas LMGN was rarely efficacious to against human epidermal growth factor receptor 2-positive/overexpression (HER2+/overexpression) breast cancer cells. The intrinsic reason for these findings was that the overexpression of fructose transporter, GLUT5, was observed in all breast cancer subtype cell lines but only a paucity of glucose transporter, GLUT1, was expressed in HER2+/overexpression breast cancer cell lines that dampened the uptake of LMGN to these cells. The cell cycle analysis indicated that the anticancer activity of LMFN was achieved by arresting cell cycle in S phase. The multiple drug effects analysis suggested the synergistic effect in the combinations of LMFN and tamoxifen to kill estrogen receptor+ breast cancer cells and LMFN and trastuzumab to kill HER2+/overexpressed breast cancer cells. Conclusion: Our work pinpoints that LMFN may be a new-onset selection for molecularly targeted therapy of breast cancers and paves the way for establishing its clinical application in the future.

Antitumor Activity and Underlying Mechanism of Phomoxanthone B in MCF7 Cells

2020 ◽  
Vol 20 ◽  
Author(s):  
Chuan Chen ◽  
Ziyue Zhao ◽  
Qian Dong ◽  
XueHui Gao ◽  
Huibin Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Antitumor Activity ◽  
Oxidative Phosphorylation ◽  
Tumor Cells ◽  
Transcriptome Analysis ◽  
Mcf7 Cells ◽  
Er Positive ◽  
Induced Apoptosis ◽  
Positive Breast Cancer

Background:: Xanthones are a class of heterocyclic natural products, which are promising sources of anticancer leads. Phomoxanthone B（PXB）and Phomoxanthone A（PXA）are xanthone dimers. PXA is well studied as an anti-cancer agent, but PXB is not. In our study, PXB was isolated from the endophytic fungus Phomopsis sp. By254. Objective:: The purpose of this study was to identify the underlying anti-tumor mechanisms of PXB in breast cancer MCF7 cell line. Methods:: Apoptosis, cell cycle, proliferation, invasion and migration assays were used to assess the antitumor activity of PXB. RNA sequencing was used to analyze the effect of PXB treatment on gene expression in MCF7 cells. Results:: PXB showed cytotoxicity toward a variety of tumor cells, especially MCF7 cells. PXB inhibited the migration and invasion, arrested cell cycle at G2/M phase and induced apoptosis associated with caspase-3 activation in MCF7 cells. The detailed transcriptome analysis revealed that PXB affected several pathways related to tumorigenesis, metabolisms-, and oxidative phosphorylation in MCF7 cells. KEGG transcriptome analysis revealed that PXB upregulated pro-survival signal pathways such as MAPK, PI3K-AKT and STAT3 pathways. We found that PXB also significantly upregulated the expression of IL24, DDIT3 and XAF1, which may contribute to PXB-induced apoptosis. We further found that PXB may downregulate oxidative phosphorylation by decreasing the expression of electron transport chain genes, especially MT-ND1, which is a potential unfavorable prognostic marker for ER-positive breast cancer. Conclusion:: PXB exerts strong cytotoxicity against human tumor cells and has a potential for ER-positive breast cancer treatment.

scholarly journals LPTO-06. A NOVEL BRAIN-PERMEANT CHEMOTHERAPEUTIC AGENT FOR THE TREATMENT OF BREAST CANCER LEPTOMENINGEAL METASTASIS

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i7-i7
Author(s):  
Jiaojiao Deng ◽  
Sophia Chernikova ◽  
Wolf-Nicolas Fischer ◽  
Kerry Koller ◽  
Bernd Jandeleit ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Tumors ◽  
Cell Lines ◽  
Chemotherapeutic Agent ◽  
Leptomeningeal Metastasis ◽  
Breast Cancer Cell Lines ◽  
Normal Brain ◽  
Breast Cancers

Abstract Leptomeningeal metastasis (LM), a spread of cancer to the cerebrospinal fluid and meninges, is universally and rapidly fatal due to poor detection and no effective treatment. Breast cancers account for a majority of LMs from solid tumors, with triple-negative breast cancers (TNBCs) having the highest propensity to metastasize to LM. The treatment of LM is challenged by poor drug penetration into CNS and high neurotoxicity. Therefore, there is an urgent need for new modalities and targeted therapies able to overcome the limitations of current treatment options. Quadriga has discovered a novel, brain-permeant chemotherapeutic agent that is currently in development as a potential treatment for glioblastoma (GBM). The compound is active in suppressing the growth of GBM tumor cell lines implanted into the brain. Radiolabel distribution studies have shown significant tumor accumulation in intracranial brain tumors while sparing the adjacent normal brain tissue. Recently, we have demonstrated dose-dependent in vitro and in vivo anti-tumor activity with various breast cancer cell lines including the human TNBC cell line MDA-MB-231. To evaluate the in vivo antitumor activity of the compound on LM, we used the mouse model of LM based on the internal carotid injection of luciferase-expressing MDA-MB-231-BR3 cells. Once the bioluminescence signal intensity from the metastatic spread reached (0.2 - 0.5) x 106 photons/sec, mice were dosed i.p. twice a week with either 4 or 8 mg/kg for nine weeks. Tumor growth was monitored by bioluminescence. The compound was well tolerated and caused a significant delay in metastatic growth resulting in significant extension of survival. Tumors regressed completely in ~ 28 % of treated animals. Given that current treatments for LM are palliative with only few studies reporting a survival benefit, Quadriga’s new agent could be effective as a therapeutic for both primary and metastatic brain tumors such as LM. REF: https://onlinelibrary.wiley.com/doi/full/10.1002/pro6.43

scholarly journals Productive Infection of Human Breast Cancer Cell Lines with Human Cytomegalovirus (HCMV)

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 641
Author(s):  
Kaitlin M. Branch ◽  
Erica C. Garcia ◽  
Yin Maggie Chen ◽  
Matthew McGregor ◽  
Mikayla Min ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Tumor ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Breast Tumor Cells

Breast cancer is the leading cause of cancer deaths among women worldwide. There are many known risk factors for breast cancer, but the role of infectious disease remains unclear. Human cytomegalovirus (HCMV) is a widespread herpesvirus that usually causes little disease. Because HCMV has been detected in breast tumor biopsy samples and is frequently transmitted via human breast milk, we investigated HCMV replication in breast tumor cells. Four human breast cancer cell lines with different expression profiles for the key diagnostic markers of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), were infected with a bacterial artificial chromosome-derived HCMV clinical strain TB40/E tagged with green fluorescent protein (GFP). Fluorescence microscopy confirmed that all four breast cancer cell lines supported virus entry. RNA was isolated from infected cells and the expression of immediate early (UL123), early (UL54), and late (UL111A) genes was confirmed using PCR. Viral proteins were detected by immunoblotting, and viral progeny were produced during the infection of breast tumor cells, as evidenced by subsequent infection of fibroblasts with culture supernatants. These results demonstrate that breast tumor cells support productive HCMV infection and could indicate that HCMV replication may play a role in breast cancer progression.

scholarly journals Triple negative aggressive phenotype controlled by miR-135b and miR-365: new theranostics candidates

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gloria Bertoli ◽  
Claudia Cava ◽  
Fabio Corsi ◽  
Francesca Piccotti ◽  
Cristina Martelli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Triple Negative ◽  
Differentially Expressed ◽  
Tumor Control ◽  
Breast Cancers ◽  
Basal Breast Cancer ◽  
Therapeutic Molecules ◽  
Invasive Capacity ◽  
Tnbc Subtype

AbstractTriple negative breast cancer (TNBC) accounts for about a fifth of all breast cancers and includes a diverse group of cancers. The heterogeneity of TNBC and the lack of target receptors on the cell surface make it difficult to develop specific therapeutic treatments. These aspects cause the high negative prognosis of patients with this type of tumor. The analysis of the molecular profiles of TNBC samples has allowed a better characterization of this tumor, supporting the search for new reliable diagnostic markers. To this end, we have developed a bioinformatic approach to integrate networks of genes differentially expressed in basal breast cancer compared to healthy tissues, with miRNAs able to regulate their expression. We studied the role of these miRNAs in TNBC subtype cell lines. We therefore identified two miRNAs, namely miR-135b and miR-365, with a central role in regulating the altered functional pathways in basal breast cancer. These two miRNAs are differentially expressed in human TNBC immunohistochemistry-selected tissues, and their modulation has been shown to play a role in the proliferation of tumor control and its migratory and invasive capacity in TNBC subtype cell lines. From the perspective of personalized medicine, we managed to modulate the expression of the two miRNAs in organotypic cultures, suggesting their possible use as diagnostic and therapeutic molecules. miR-135b and miR-365 have a key role in TNBC, controlling proliferation and invasion. Their detection could be helpful in TNBC diagnosis, while their modulation could become a new therapeutic tool for TNBC.

scholarly journals A chemical screen in diverse breast cancer cell lines reveals genetic enhancers and suppressors of sensitivity to PI3K isoform-selective inhibition

2008 ◽  
Vol 415 (1) ◽  
pp. 97-110 ◽  
Author(s):  
Neil E. Torbett ◽  
Antonio Luna-Moran ◽  
Zachary A. Knight ◽  
Andrew Houk ◽  
Mark Moasser ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Therapeutics ◽  
Cancer Cell Lines ◽  
Genetic Alterations ◽  
Breast Cancer Cell Lines ◽  
Selective Inhibitors

The PI3K (phosphoinositide 3-kinase) pathway regulates cell proliferation, survival and migration and is consequently of great interest for targeted cancer therapy. Using a panel of small-molecule PI3K isoform-selective inhibitors in a diverse set of breast cancer cell lines, we have demonstrated that the biochemical and biological responses were highly variable and dependent on the genetic alterations present. p110α inhibitors were generally effective in inhibiting the phosphorylation of PKB (protein kinase B)/Akt and S6, two downstream components of PI3K signalling, in most cell lines examined. In contrast, p110β-selective inhibitors only reduced PKB/Akt phosphorylation in PTEN (phosphatase and tensin homologue deleted on chromosome 10) mutant cell lines, and was associated with a lesser decrease in S6 phosphorylation. PI3K inhibitors reduced cell viability by causing cell-cycle arrest in the G1 phase, with multi-targeted inhibitors causing the most potent effects. Cells expressing mutant Ras were resistant to the cell-cycle effects of PI3K inhibition, which could be reversed using inhibitors of Ras signalling pathways. Taken together, our data indicate that these compounds, alone or in suitable combinations, may be useful as breast cancer therapeutics, when used in appropriate genetic contexts.

A truncated intracellular HER2/neu receptor produced by alternative RNA processing affects growth of human carcinoma cells

1993 ◽  
Vol 13 (4) ◽  
pp. 2247-2257
Author(s):  
G K Scott ◽  
R Robles ◽  
J W Park ◽  
P A Montgomery ◽  
J Daniel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Cell Lines ◽  
Rna Processing ◽  
Human Tumor ◽  
Full Length ◽  
Splice Donor Site ◽  
Breast Cancer Cell Lines ◽  
Her2 Receptor ◽  
Human Carcinoma

Cloned sequences encoding a truncated form of the HER2 receptor were obtained from cDNA libraries derived from two HER2-overexpressing human breast cancer cell lines, BT-474 and SK-BR-3. The 5' 2.1 kb of the encoded transcript is identical to that of full-length 4.6-kb HER2 transcript and would be expected to produce a secreted form of HER2 receptor containing only the extracellular ligand binding domain (ECD). The 3' end of the truncated transcript diverges 61 nucleotides before the receptor's transmembrane region, reads through a consensus splice donor site containing an in-frame stop codon, and contains a poly(A) addition site, suggesting that the truncated transcript arises by alternative RNA processing. S1 nuclease protection assays show a 40-fold variation in the abundance of the truncated 2.3-kb transcript relative to full-length 4.6-kb transcript in a panel of eight HER2-expressing tumor cell lines of gastric, ovarian, and breast cancer origin. Expression of this truncated transcript in COS-1 cells produces both secreted and intracellular forms of HER2 ECD; however, immunofluorescent labeling of HER2 ECD protein in MKN7 tumor cells that natively overexpress the 2.3-kb transcript suggests that transcriptionally generated HER2 ECD is concentrated within the perinuclear cytoplasm. Metabolic labeling and endoglycosidase studies suggest that this HER2 ECD (100 kDa) undergoes differential trafficking between the endoplasmic reticulum and Golgi compartments compared with full-length (185-kDa) HER2 receptor. Transfection studies indicate that excess production of HER2 ECD in human tumor cells overexpressing full-length HER2 receptor can result in resistance to the growth-inhibiting effects of anti-HER2 monoclonal antibodies such as muMAb4D5. These findings demonstrate alternative processing of the HER2 transcript and implicate a potentially important growth regulatory role for intracellularly sequestered HER2 ECD in HER2-amplified human tumors.

scholarly journals Current Approaches and Emerging Directions in HER2-resistant Breast Cancer

2014 ◽  
Vol 8 ◽  
pp. BCBCR.S9453 ◽  
Author(s):  
Adam M. Brufsky
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Molecular Mechanisms ◽  
Mammalian Target Of Rapamycin ◽  
Growth Factor Receptor ◽  
Initial Response ◽  
Her2 Overexpression ◽  
Breast Cancers ◽  
Intrinsic Resistance ◽  
Her2 Positive

Human epidermal growth factor receptor-2 (HER2) is overexpressed in up to 30% of breast cancers; HER2 overexpression is indicative of poor prognosis. Trastuzumab, an anti-HER2 monoclonal antibody, has led to improved outcomes in patients with HER2-positive breast cancer, including improved overall survival in adjuvant and first-line settings. However, a large proportion of patients with breast cancer have intrinsic resistance to HER2-targeted therapies, and nearly all become resistant to therapy after initial response. Elucidation of underlying mechanisms contributing to HER2 resistance has led to development of novel therapeutic strategies, including those targeting HER2 and downstream pathways, heat shock protein 90, telomerase, and vascular endothelial growth factor inhibitors. Numerous clinical trials are ongoing or completed, including phase 3 data for the mammalian target of rapamycin inhibitor everolimus in patients with HER2-resistant breast cancer. This review considers the molecular mechanisms associated with HER2 resistance and evaluates the evidence for use of evolving strategies in patients with HER2-resistant breast cancer.

scholarly journals Thymoquinone-Loaded Nanostructured Lipid Carrier Exhibited Cytotoxicity towards Breast Cancer Cell Lines (MDA-MB-231 and MCF-7) and Cervical Cancer Cell Lines (HeLa and SiHa)

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Wei Keat Ng ◽  
Latifah Saiful Yazan ◽  
Li Hua Yap ◽  
Wan Abd Ghani Wan Nor Hafiza ◽  
Chee Wun How ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Nanostructured Lipid Carrier ◽  
Cycle Arrest ◽  
Mcf 7

Thymoquinone (TQ) has been shown to exhibit antitumor properties. Thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) was developed to improve the bioavailability and cytotoxicity of TQ. This study was conducted to determine the cytotoxic effects of TQ-NLC on breast cancer (MDA-MB-231 and MCF-7) and cervical cancer cell lines (HeLa and SiHa). TQ-NLC was prepared by applying the hot high pressure homogenization technique. The mean particle size of TQ-NLC was 35.66 ± 0.1235 nm with a narrow polydispersity index (PDI) lower than 0.25. The zeta potential of TQ-NLC was greater than −30 mV. Polysorbate 80 helps to increase the stability of TQ-NLC. Differential scanning calorimetry showed that TQ-NLC has a melting point of 56.73°C, which is lower than that of the bulk material. The encapsulation efficiency of TQ in TQ-NLC was 97.63 ± 0.1798% as determined by HPLC analysis. TQ-NLC exhibited antiproliferative activity towards all the cell lines in a dose-dependent manner which was most cytotoxic towards MDA-MB-231 cells. Cell shrinkage was noted following treatment of MDA-MB-231 cells with TQ-NLC with an increase of apoptotic cell population (P<0.05). TQ-NLC also induced cell cycle arrest. TQ-NLC was most cytotoxic towards MDA-MB-231 cells. It induced apoptosis and cell cycle arrest in the cells.

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