scholarly journals Hirudin Suppresses Metastasis of Human Breast Adenocarcinoma Cells In Vitro and in a Zebrafish Xenograft Model

2021 ◽  
Author(s):  
Shuo Zhang ◽  
Lei Zhou ◽  
XiaoYan Jiang ◽  
HongHui Ni ◽  
ShuiYing Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Adhesion ◽  
Xenograft Model ◽  
Cell Counting ◽  
Breast Adenocarcinoma ◽  
Antitumor Effects ◽  
Adenocarcinoma Cells ◽  
Proliferation And Metastasis ◽  
Mcf 7

Abstract Background: Breast cancer is the leading cause of cancer-related death in women worldwide. Hirudin has been shown to inhibit the growth and metastasis of several types of cancers in experimental tumor models. However, whether hirudin exerts antitumor effects on breast adenocarcinoma cells has not yet been investigated. The objective of this study was to evaluate the antitumor effects and explore the underlying mechanisms of hirudin in breast adenocarcinoma MCF-7 cells. Methods: The viability of MCF-7 cells was assayed by Cell Counting Kit-8. The adhesion ability of the cells was evaluated by cell adhesion assay. Besides, cell migration was detected by wound healing assay. Cell invasion was examined using Transwell chamber assay. The underlying molecular mechanism was investigated by immunofluorescence. In addition, In vivo zebrafish xenograft model was used to verify the proliferation and metastasis of hirudin on MCF-7 cells. Results: The results showed that hirudin significantly inhibited the cell viability and suppressed cell adhesion, migration, invasion compared with the control group. Importantly, hirudin significantly decreased the expression of CHD1L, MDM2 protein, and increased the expression of p53 protein. Moreover, the zebrafish xenograft study revealed that hirudin inhibited the proliferation and metastasis of MCF-7 cells in vivo. Conclusion: The present findings demonstrate that hirudin suppressed metastasis of MCF-7 cells and the mechanism may involve with the CHD1L/MDM2/p53 axis. Hirudin is a promising antineoplastic agent for the treatment of breast cancer with significant antimetastatic activities. Keywords: Breast cancer, Hirudin, Metastasis, Zebrafish, CHD1L

In vitro evaluation of estrogenic, antiestrogenic and antitumor effects of amentoflavone

2021 ◽  
pp. 096032712199945
Author(s):  
AT Aliyev ◽  
S Ozcan-Sezer ◽  
A Akdemir ◽  
H Gurer-Orhan
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Antitumor Effects ◽  
Antiestrogenic Activity ◽  
Er Positive ◽  
In Vivo Effects ◽  
Mcf 7

Apigenin, a flavonoid, is reported to act as an estrogen receptor (ER) agonist and inhibit aromatase enzyme. However, amentoflavone, a biflavonoid bearing two apigenin molecules, has not been evaluated for its endocrine modulatory effects. Besides, it is highly consumed by young people to build muscles, enhance mood and lose weight. In the present study, apigenin was used as a reference molecule and ER mediated as well as ER-independent estrogenic/antiestrogenic activity of amentoflavone was investigated. Antitumor activity of amentoflavone was also investigated in both ER positive (MCF-7 BUS) and triple-negative (MDA-MB-231) breast cancer cells and its cytotoxicity was evaluated in human breast epithelial cells (MCF-10A). Our data confirmed ER agonist, aromatase inhibitory and cytotoxic effects of apigenin in breast cancer cells, where no ER mediated estrogenic effect and physiologically irrelevant, slight, aromatase inhibition was found for amentoflavone. Although selective cytotoxicity of amentoflavone was found in MCF-7 BUS cells, it does not seem to be an alternative to the present cytotoxic drugs. Therefore, neither an adverse effect, mediated by an estrogenic/antiestrogenic effect of amentoflavone nor a therapeutical benefit would be expected from amentoflavone. Further studies could be performed to investigate its in vivo effects.

New targeted anti CDK4/6 peptide MM-D37K.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13545-e13545 ◽  
Author(s):  
Vladimir Konstantinovich Bozhenko ◽  
Tatyana Michailovna Kulinich ◽  
Elena Aleksandrovna Kudinova ◽  
Andrey Boldyrev ◽  
Vladimir Alekseevich Solodkij
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Full Range ◽  
Mrna Level ◽  
Xenograft Model ◽  
Specific Inhibitor ◽  
Antitumor Effects ◽  
Mcf 7

e13545 Background: MM-D37K is a synthetic peptide which consists of p16INK4a-specific inhibitor of complex cyclin D- CDK4 and CDK6 and cell penetrating peptide (CPP) – Antp (Penetratin). We investigated in vitro and in vivo cytotoxic, cytostatic and antitumor activity of MM-D37K. The level of cyclin A, Ki67,bax, bcl-2 and pRb phosphorylation was investigated. Full range of Toxicology tests and Pharmacokinetics experiments in mice, rats and rabbits were performed. Methods: Different cell lines (Jurcat, Raji, A549, MCF-7, Hct-116, Ht-29, HEK293) were incubated with 0.1-100 mM MM-D37K for 24-48 hrs. Proliferation (MTT), DNA-content, cell cycle (flow cytometry) and mRNA level of appropriate proteins (RT PCR) were investigated. In vivo experiments were conducted on xenograft model of HCT116, A-549 at concentration 5 and 10 mg/kg of MM-D37K. Toxicology experiments were made under RF Law and included 3 types of animals. LC-MS MMD37K method of detection in plasma was developed. Results: MM-D37K prevented pRb phosphorilation and proliferation activation in all investigated cell lines. Cell cycle was blocked in G1 phase. Cytostatic effect did not depend on p16 mutation or expression. MM-D37K induced apoptosis in 20-82% of investigated cells at 40 mM with lowest level for MCF-7. LD10 for rats was 100 mg/kg and no deaths were registered for rabbits (highest dose was 50 mg/kg). Concentration of MMD-37K in plasma after 2 min and bolus i.v. injection in dose 10 mg/kg was 72.16±5.64 mcg/ml. Concentration decreased in two phases. 1st – t1/2 = 2.39±0.39 min and for 2nd t1/2=2.39±0.39 hr. Antitumor effects in xenograft model were 53% for A-549 and 67% for HCT116. Conclusions: Our results proved cytotoxic, cytostatic and antitumor effects of MM-D37K in investigated cell lines in vitro and in vivo. Toxicological and pharmacokinetics results allow us recommend for I/IIa Phase clinical trial. (Support: MetaMax Ltd., RFFI, Minpromtorg RF.)

scholarly journals Enhanced Anti-Tumor Effect of Folate-Targeted FA-AMA-hyd-DOX Conjugate in a Xenograft Model of Human Breast Cancer

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7110
Author(s):  
Tian-tian Liao ◽  
Jiang-fan Han ◽  
Fei-yue Zhang ◽  
Ren Na ◽  
Wei-liang Ye
Keyword(s):  
Breast Cancer ◽  
Nude Mice ◽  
Folate Receptor ◽  
Xenograft Model ◽  
Maximum Tolerated Dose ◽  
Therapeutic Drug ◽  
Antitumor Effects ◽  
Tumor Bearing

Folate-aminocaproic acid-doxorubicin (FA-AMA-hyd-DOX) was firstly synthesized by our group. It was indicated that FA-AMA-hyd-DOX was pH-responsive, and had strong cytotoxicity on a folate receptor overexpressing cell line (KB cells) in vitro. The aim of our study was to further explore the potential use of FA-AMA-hyd-DOX as a new therapeutic drug for breast cancer. The cellular uptake and the antiproliferative activity of the FA-AMA-hyd-DOX in MDA-MB-231 cells were measured. Compared with DOX, FA-AMA-hyd-DOX exhibited higher targeting ability and cytotoxicity to FR-positive tumor cells. Subsequently, the tissue distribution of FA-AMA-hyd-DOX was studied, and the result confirmed that DOX modified by FA can effectively increase the selectivity of drugs in vivo. After determining the maximum tolerated dose (MTD) of FA-AMA-hyd-DOX in MDA-MB-231 tumor-bearing nude mice, the antitumor effects and the in vivo safety of FA-AMA-hyd-DOX were systematically evaluated. The data showed that FA-AMA-hyd-DOX could effectively increase the dose of DOX tolerated by tumor-bearing nude mice and significantly inhibit MDA-MB-231 tumor growth in vivo. Furthermore, FA-AMA-hyd-DOX treatment resulted in almost no obvious damage to the mice. All the positive data suggest that FA-targeted FA-AMA-hyd-DOX is a promising tumor-targeted compound for breast cancer therapy.

scholarly journals Elevated Expression of The Rhythm Gene NFIL3 Promotes The Progression of TNBC By Activating NF-κB Signaling Through Suppression of NFKBIA Transcription

2021 ◽  
Author(s):  
Wei-Wei Yang ◽  
Jing Li ◽  
Minghui Zhang ◽  
Haichuan Yu ◽  
Yuan Zhuang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Epidemiological Studies ◽  
Tumor Formation ◽  
Cell Counting ◽  
Aberrant Expression ◽  
Functional Studies ◽  
Proliferation And Metastasis

Abstract Background: Epidemiological studies have confirmed that abnormal circadian rhythms are associated with tumorigenesis in breast cancer. However, few studies have investigated the pathological roles of rhythm genes in breast cancer progression. Methods: The expressions of NFIL3 and NFKBIA were measured by Western blot, qRT–PCR and IHC analysis. The proliferation and metastasis of two TNBC cell lines were analyzed by cell counting assays, clone formation assays, subcutaneous tumor formation assay, wound healing assays, transwell assays and the mouse tail vein injection model.Results: We evaluated the aberrant expression of 32 rhythm genes in breast cancer and identified that nuclear factor interleukin 3 regulated (NFIL3) expression is significantly altered in triple-negative breast cancer (TNBC). We found that NFIL3 inhibits its own transcription, and thus, downregulated NFIL3 mRNA indicates high expression of NFIL3 protein in breast cancer. Functional studies demonstrated that NFIL3 promotes the proliferation and metastasis of TNBC cells in vitro and in vivo. Higher expression of NFIL3 is associated with poor prognosis of patients with TNBC. Gene enrichment assays revealed that NFIL3 primarily regulates cancer-associated inflammation. Correlation analysis showed that expression of NFIL3 is associated with infiltration level of various immune cells in breast cancer. We further demonstrated that NFIL3 enhances the activity of NF-κB signaling. Mechanistically, we revealed that NFIL3 directly suppresses the transcription of NFKBIA, which blocks the activation of NF-κB and inhibits the progression of TNBC cells in vitro and in vivo. Moreover, we showed that enhancing NF-κB activity by repressing NFKBIA largely mimics the oncogenic effect of NFIL3 in TNBC, and anti-inflammatory strategies targeting NF-κB activity block the oncogenic roles of NFIL3 in TNBC. Conclusion:NFIL3 promotes the progression of TNBC by suppressing NFKBIA and then enhancing NF-κB signaling-mediated cancer-associated inflammation. This study may provide a new target for TNBC prevention and therapy.

scholarly journals The Potential Utility of Curcumin in the Treatment of HER-2-Overexpressed Breast Cancer: AnIn VitroandIn VivoComparison Study with Herceptin

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Hung-Wen Lai ◽  
Su-Yu Chien ◽  
Shou-Jen Kuo ◽  
Ling-Ming Tseng ◽  
Hui-Yi Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signal Transduction ◽  
Cell Growth ◽  
Xenograft Model ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Her 2 ◽  
Mcf 7

HER-2 is an important oncoprotein overexpressed in about 15–25% of breast cancers. We hypothesized that the ability of curcumin to downregulate HER-2 oncoprotein and inhibit the signal transduction pathway of PI3K/Akt, MAPK, and NF-κB activation may be important in the treatment of HER-2-overexpressed breast cancer. To examine the effect of curcumin on breast cancer cells, MCF-7, MDA-MB-231, MCF-10A, BT-474, and SK-BR-3-hr (a herceptin resistant strain from SK-BR-3) cells were used forin vitroanalysis. Thein vivoeffect of curcumin on HER-2-overexpressed breast cancer was investigated with the HER-2-overexpressed BT-474 xenograft model. Cell growth, cell cycle change, the antimobility effect, signal transduction, and xenograft volume analysis between groups treated with herceptin and/or curcumin were tested. Curcumin decreased the cell growth of various breast cancer cell lines (MCF-7, MDA-MB-231, MCF-10A, BT-474, and SK-BR-3-hr). In Western blot analysis, the phosphorylation of Akt, MAPK, and expression of NF-κB were reduced in BT-474 cells, but not in SK-BR-3-hr cells, after treatment with herceptin. When treated with curcumin, the HER-2 oncoprotein, phosphorylation of Akt, MAPK and expression of NF-κB were decreased in both BT-474 and SK-BR-3-hr cells. In the BT-474 xenograft model, though not as much as herceptin, curcumin did effectively decrease the tumor size. The combination of curcumin with herceptin was not better than herceptin alone; however, the combination of taxol and curcumin had an antitumor effect comparable with taxol and herceptin. The results suggested that curcumin has potential as a treatment for HER-2-overexpressed breast cancer.

scholarly journals Analysis and Identification of Active Compounds from Gami-Soyosan Toxic to MCF-7 Human Breast Adenocarcinoma Cells

Biomolecules ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 272 ◽  
Author(s):  
Mi-Yeon Jung ◽  
Chang-Seob Seo ◽  
Seon-Eun Baek ◽  
Jaemin Lee ◽  
Myoung-Sook Shin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gallic Acid ◽  
Parp Cleavage ◽  
Breast Adenocarcinoma ◽  
Human Breast ◽  
Human Breast Adenocarcinoma ◽  
Decursinol Angelate ◽  
Adenocarcinoma Cells ◽  
Er Positive ◽  
Mcf 7

Gami-soyosan is a medicinal herbal formulation prescribed for the treatment of menopausal symptoms, including hot flashes and osteoporosis. Gami-soyosan is also used to treat similar symptoms experienced by patients with breast cancer. The incidence of breast cancer in women receiving hormone replacement therapy is a big burden. However, little is known about the components and their mechanism of action that exhibit these beneficial effects of Gami-soyosan. The aim of this study was to simultaneously analyze compounds of Gami-soyosan, and determine their cytotoxic effects on estrogen receptor (ER)-positive MCF-7 human breast adenocarcinoma cells. We established a simultaneous analysis method of 18 compounds contained in Gami-soyosan and found that, among the various compounds in Gami-soyosan, gallic acid (1), decursin (17), and decursinol angelate (18) suppressed the viability of MCF-7 cells. Gallic acid (1), decursin (17), and decursinol angelate (18) induced apoptotic cell death and significantly increased poly (ADP-ribose) polymerase (PARP) cleavage and the Bcl-2-associated X protein/ B-cell lymphoma 2 (Bax/Bcl-2) ratio. Decursin (17) increased the expression of cleaved caspases-8, -9, -7, and -3. Decursinol angelate (18) increased the expression of cleaved caspase-8 and -7. These three components altered the different apoptosis signal pathways. Collectively, gallic acid (1), decursin (17), and decursinol angelate (18) may be used to inhibit cell proliferation synergistically in patients with ER-positive breast cancer.

scholarly journals MPPa-PDT suppresses breast tumor migration/invasion by inhibiting Akt-NF-κB-dependent MMP-9 expression via ROS

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Liyi Huang ◽  
Haidan Lin ◽  
Qing Chen ◽  
Lehua Yu ◽  
Dingqun Bai
Keyword(s):  
Breast Cancer ◽  
Tumor Metastasis ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Ros Generation ◽  
High Morbidity ◽  
Matrigel Invasion Assay ◽  
Matrigel Invasion ◽  
Mcf 7

Abstract Background Breast cancer is one of the most commonly diagnosed cancers in women, with high morbidity and mortality. Tumor metastasis is implicated in most breast cancer deaths; thus, inhibiting metastasis may provide a therapeutic direction for breast cancer. In the present study, pyropheophorbide-α methyl ester-mediated photodynamic therapy (MPPa-PDT) was used to inhibit metastasis in MCF-7 breast cancer cells. Methods Uptake of MPPa was detected by fluorescence microscopy. Cell viability was evaluated by the Cell Counting Kit-8 (CCK-8). ROS generation was detected by 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA). The migration of cells was assessed by wound healing assay, and invasion ability was assessed by Matrigel invasion assay. Levels of MMP2 and MMP9 were measured by PCR. Akt, phospho-Akt (Ser473), phospho-NF-κB p65 (Ser536) and NF-κB p65 were measured by western blotting. The F-actin cytoskeleton was observed by immunofluorescence. Lung tissue was visualized by hematoxylin and eosin staining. Results Following MPPa-PDT, migration and invasion were decreased in the MCF-7 cells. MPPa-PDT downregulated the expression of MMP2 and MMP9, which are responsible for the initiation of metastasis. MPPa-PDT reduced the phosphorylation of Akt and NF-κB. MPPa-PDT also reduced the expression of F-actin in cytoskeleton in MCF-7 cells. These effects were blocked by the reactive oxygen species scavenger NAC or the Akt activator SC79, while the PI3K inhibitor LY294002 or the Akt inhibitor triciribine enhanced these effects. Moreover, MPPa-PDT inhibited tumor metastasis and destroyed F-actin in vivo. Conclusion Taken together, these results demonstrate that MPPa-PDT inhibits the metastasis of MCF-7 cells both in vitro and in vivo and may be involved in the Akt/NF-κB-dependent MMP-9 signaling pathway. Thus, MPPa-PDT may be a promising treatment to inhibit metastasis.

Recombinant human PDCD5 protein enhances chemosensitivity of breast cancer in vitro and in vivo

2013 ◽  
Vol 91 (6) ◽  
pp. 526-531 ◽  
Author(s):  
Lanlan Wang ◽  
Changjun Wang ◽  
Bingnan Su ◽  
Quansheng Song ◽  
Yingmei Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Intraperitoneal Administration ◽  
Xenograft Model ◽  
Cell Types ◽  
Antitumor Effects ◽  
Protein Levels

Resistance to paclitaxel is common for treatment of breast cancer. Programmed cell death 5 (PDCD5) accelerates apoptosis in different cell types in response to various stimuli; moreover PDCD5 has been shown to be down-regulated in many tumors. In this study, protein levels of PDCD5 were found to be up-regulated in paclitaxel-treated MDA-MB-231 breast cancer cells. MTT, CCK-8, and clonogenic assays have shown that recombinant human PDCD5 (rhPDCD5) alone could not produce an obvious growth inhibition. However, upon paclitaxel triggering apoptosis, rhPDCD5 protein potentiated chemotherapeutic drugs-induced growth arrest in MDA-MB-231, SK-BR-3, and ZR-75-1 breast cancer cells. In vivo, we use a human breast cancer xenograft model to study. We found that rhPDCD5 dramatically improves the antitumor effects of paclitaxel treatment by intraperitoneal administration. These data suggest that rhPDCD5 has the potential to use as a therapeutic agent to enhance the paclitaxel sensitivity of breast cancer cells.

Sign in / Sign up

Export Citation Format

Share Document