scholarly journals GDF5 Regulates TGFß-Dependent Angiogenesis in Breast Carcinoma MCF-7 Cells: In Vitro and In Vivo Control by Anti-TGFß Peptides

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e50342 ◽  
Author(s):  
Francesca Margheri ◽  
Nicola Schiavone ◽  
Laura Papucci ◽  
Lucia Magnelli ◽  
Simona Serratì ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Mcf 7

scholarly journals A newfangled coordinated ruthenium phloretin complex reprogramming breast cancer microenvironment interceded by modulation of PI3K/Akt/mTOR/VEGF pathway and modifying the antioxidant status correlated with intensified apoptotic events.

2020 ◽  
Author(s):  
Chenyang He ◽  
Guo Yu ◽  
Anil Kumar Mondru ◽  
Tania Chakraborty ◽  
Souvik Roy
Keyword(s):  
Breast Carcinoma ◽  
Cell Lines ◽  
Human Cancer ◽  
In Vivo Model ◽  
Human Cancer Cell Lines ◽  
Vegf Pathway ◽  
Breast Carcinoma Cell Lines ◽  
Mcf 7

Abstract Background: Our recent investigation directed to synthesize and characterize a novel ruthenium– phloretin complex accompanied by the study of antioxidant in addition to DNA binding capabilities, and to determine the chemotherapeutic activity against breast carcinoma in vitro and in vivo approach.Methods: Ruthenium–phloretin complex was synthesized and characterized using various spectroscopic methods. The complex was further investigated to determine its efficacy in both MCF-7 and MDA-MB-231 human cancer cell lines and finally in an in vivo model of DMBA induced mammary carcinogenesis in ratsResults: Our studies confirm that the chelation of the metal and ligand was materialize by the 3-OH and 9-OH functional groups of the ligand and the complex is found crystalline and was capable of intercalating with CT-DNA. The complex was capable of reducing cellular propagation and initiate apoptotic events in MCF-7 and MDA-MB-231 breast carcinoma cell lines. Additionally, ruthenium-phloretin complex could modulate p53 intervene apoptosis in the breast carcinoma, initiated by the intrinsic apoptotic trail facilitated by the Bcl2 and Bax and at the same time down regulating the PI3K/Akt/mTOR pathway coupled with MMP9 regulated tumor invasive pathways.Conclusions: Ruthenium-phloretin chemotherapy could interrupt, revoke or suspend the succession of breast carcinoma by altering intrinsic apoptosis along with the antiangiogenic pathway, hence fulfilling the role of a prospective candidate in cancer chemotherapeutics in the in the near future.

scholarly journals A Newfangled Coordinated Ruthenium Phloretin Complex Reprogramming Breast Cancer Microenvironment Interceded by Modulation of PI3K/Akt/Mtor/VEGF Pathway and Modifying The Antioxidant Status Correlated With Intensified Apoptotic Events.

2020 ◽  
Author(s):  
Chenyang He ◽  
Junli Wang ◽  
Tania Chakraborty ◽  
Souvik Roy
Keyword(s):  
Breast Carcinoma ◽  
Cell Lines ◽  
Human Cancer ◽  
In Vivo Model ◽  
Human Cancer Cell Lines ◽  
Vegf Pathway ◽  
Breast Carcinoma Cell Lines ◽  
Mcf 7

Abstract Background: Our recent investigation directed to synthesize and characterize a novel ruthenium– phloretin complex accompanied by the study of antioxidant in addition to DNA binding capabilities, and to determine the chemotherapeutic activity against breast carcinoma in vitro and in vivo approach.Methods: Ruthenium–phloretin complex was synthesized and characterized using various spectroscopic methods. The complex was further investigated to determine its efficacy in both MCF-7 and MDA-MB-231 human cancer cell lines and finally in an in vivo model of DMBA induced mammary carcinogenesis in ratsResults: Our studies confirm that the chelation of the metal and ligand was materialize by the 3-OH and 9-OH functional groups of the ligand and the complex is found crystalline and was capable of intercalating with CT-DNA. The complex was capable of reducing cellular propagation and initiate apoptotic events in MCF-7 and MDA-MB-231 breast carcinoma cell lines. Additionally, ruthenium-phloretin complex could modulate p53 intervene apoptosis in the breast carcinoma, initiated by the intrinsic apoptotic trail facilitated by the Bcl2 and Bax and at the same time down regulating the PI3K/Akt/mTOR pathway coupled with MMP9 regulated tumor invasive pathways.Conclusions: Ruthenium-phloretin chemotherapy could interrupt, revoke or suspend the succession of breast carcinoma by altering intrinsic apoptosis along with the antiangiogenic pathway, hence fulfilling the role of a prospective candidate in cancer chemotherapeutics in the in the near future.

Erythropoietic Therapy Does Not Stimulate Tumor Growth in Erythropoietin Receptor (EPOR)-Positive MDA-MB-231 and MCF-7 Breast Carcinoma Models.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4260-4260 ◽  
Author(s):  
Kenneth R. LaMontagne ◽  
Jeannene Butler ◽  
Deborah Marshall ◽  
Jennifer Tullai ◽  
Ze’ev Gechtman ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Tumor Growth ◽  
Cell Lines ◽  
Darbepoetin Alfa ◽  
Epoetin Alfa ◽  
Epoetin Beta ◽  
Epor Expression ◽  
Mcf 7

Abstract Recombinant epoetins (epoetin alfa, darbepoetin alfa, epoetin beta) increase hemoglobin (Hb), reduce transfusions, and improve quality of life in patients with chemotherapy-related anemia. However, results from 2 phase III trials reporting lower survival rates relative to placebo in cancer patients treated with recombinant epoetins beyond anemia correction (ie, to Hb >12 g/dL) (Leyland-Jones. Lancet Oncol 2003; Henke et al. Lancet 2003) have prompted further investigation into the potential proliferative action of these agents on non-erythroid cells, including tumor cells, which express EPOR. The current analyses evaluated the clinical significance of EPOR expression after in vitro administration of recombinant human erythropoietin (rHuEPO, epoetin alfa), as well as the in vivo effect of recombinant epoetins on tumor growth, in 2 well-established preclinical models of breast carcinoma (MDA-MB-231 and MCF-7 cell lines). The in vitro analysis evaluated EPOR expression under hypoxic and normoxic conditions by immunoblotting, flow cytometry, and immunohistochemistry. EPOR binding was assessed with radioactive iodine-labeled rHuEPO (125I-rHuEPO). The in vivo analysis evaluated the effect of recombinant epoetin therapy on tumor growth in orthotopically implanted MDA-MB-231 and MCF-7 breast carcinoma xenograft models in athymic mice. Mice received 1 of 4 treatments: saline (control) every other day (QOD), 0.0025 mg/kg epoetin alfa subcutaneously (SC) QOD, 0.0075 mg/kg darbepoetin alfa SC once weekly, and 0.0025 mg/kg epoetin beta SC QOD. Effect on tumor growth was measured by calculating the difference in the final (Day 23) mean tumor volume between the treated group and the control group. Both cell lines demonstrated EPOR staining almost exclusively in the cytosol, with minimal cell surface expression. Intracellular EPOR was comparable under normoxic and hypoxic conditions, and hypoxia did not affect the expression or localization of EPOR. Epoetin alfa did not stimulate the migration, proliferation, or activation of signal transduction cascades in the 2 breast cancer models, although these pathways are normally activated in hematopoietic cells. There was no significant effect on tumor volume after 23 days of recombinant epoetin therapy compared with control. Mean tumor volumes ± standard error (SE) in the MDA-MB-231 cells on Day 23 were as follows: control, 847.6 ± 91.9 mm3; epoetin alfa, 560.6 ± 57.4 mm3; darbepoetin alfa, 809.8 ± 129.9 mm3; epoetin beta, 730.7 ± 66.4 mm3. In the MCF-7 cells, mean tumor volumes ± SE, respectively, were 1004.3 ± 72.9 mm3, 914.5 ± 245 mm3, 884.5 ± 97.1 mm3, and 809.4 ± 103.3 mm3. Recombinant epoetin therapy did not affect tumor inhibition or survival when coadministered with paclitaxel. In both cell lines, recombinant epoetin therapy resulted in mean final Hb values that were significantly (P<.01) higher than those observed with control (all agents produced Hb increases >1.0 g/dL/week), validating that pharmacologic doses were administered. Our findings suggest that although EPOR was expressed, it was nonfunctional and not involved in tumor growth promotion in these 2 models of breast carcinoma.

scholarly journals Anticancer Activities of Thymus vulgaris L. in Experimental Breast Carcinoma in Vivo and in Vitro

2019 ◽  
Vol 20 (7) ◽  
pp. 1749 ◽  
Author(s):  
Kubatka ◽  
Uramova ◽  
Kello ◽  
Kajo ◽  
Samec ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Methylation Status ◽  
Thymus Vulgaris ◽  
Control Analysis ◽  
Gene Promoters ◽  
Antitumor Effects ◽  
Mammary Carcinomas ◽  
Mcf 7

Naturally-occurring mixtures of phytochemicals present in plant foods are proposed to possess tumor-suppressive activities. In this work, we aimed to evaluate the antitumor effects of Thymus vulgaris L. in in vivo and in vitro mammary carcinoma models. Dried T. vulgaris (as haulm) was continuously administered at two concentrations of 0.1% and 1% in the diet in a chemically-induced rat mammary carcinomas model and a syngeneic 4T1 mouse model. After autopsy, histopathological and molecular analyses of rodent mammary carcinomas were performed. In addition, in vitro evaluations using MCF-7 and MDA-MB-231 cells were carried out. In mice, T. vulgaris at both doses reduced the volume of 4T1 tumors by 85% (0.1%) and 84% (1%) compared to the control, respectively. Moreover, treated tumors showed a substantial decrease in necrosis/tumor area ratio and mitotic activity index. In the rat model, T. vulgaris (1%) decreased the tumor frequency by 53% compared to the control. Analysis of the mechanisms of anticancer action included well-described and validated diagnostic and prognostic markers that are used in both clinical approach and preclinical research. In this regard, the analyses of treated rat carcinoma cells showed a CD44 and ALDH1A1 expression decrease and Bax expression increase. Malondialdehyde (MDA) levels and VEGFR-2 expression were decreased in rat carcinomas in both the T. vulgaris treated groups. Regarding the evaluations of epigenetic changes in rat tumors, we found a decrease in the lysine methylation status of H3K4me3 in both treated groups (H3K9m3, H4K20m3, and H4K16ac were not changed); up-regulations of miR22, miR34a, and miR210 expressions (only at higher doses); and significant reductions in the methylation status of four gene promoters—ATM serin/threonine kinase, also known as the NPAT gene (ATM); Ras-association domain family 1, isoform A (RASSF1); phosphatase and tensin homolog (PTEN); and tissue inhibitor of metalloproteinase-3 (TIMP3) (the paired-like homeodomain transcription factor (PITX2) promoter was not changed). In vitro study revealed the antiproliferative and proapoptotic effects of essential oils of T. vulgaris in MCF-7 and MDA-MB-231 cells (analyses of 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS); 5-bromo-20-deoxyuridine (BrdU); cell cycle; annexin V/PI; caspase-3/7; Bcl-2; PARP; and mitochondrial membrane potential). T. vulgaris L. demonstrated significant chemopreventive and therapeutic activities against experimental breast carcinoma.

scholarly journals Chemopreventive and Therapeutic Efficacy of Cinnamomum zeylanicum L. Bark in Experimental Breast Carcinoma: Mechanistic In Vivo and In Vitro Analyses

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1399 ◽  
Author(s):  
Peter Kubatka ◽  
Martin Kello ◽  
Karol Kajo ◽  
Marek Samec ◽  
Karin Jasek ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Essential Oil ◽  
Caspase 3 ◽  
Methylation Status ◽  
Cinnamomum Zeylanicum ◽  
Dose Dependent ◽  
Rat Tumor ◽  
Mcf 7

Comprehensive oncology research suggests an important role of phytochemicals or whole plant foods in the modulation of signaling pathways associated with anticancer action. The goal of this study is to assess the anticancer activities of Cinnamomum zeylanicum L. using rat, mouse, and cell line breast carcinoma models. C. zeylanicum (as bark powder) was administered in the diet at two concentrations of 0.1% (w/w) and 1% (w/w) during the whole experiment in chemically induced rat mammary carcinomas and a syngeneic 4T1 mouse model. After autopsy, histopathological and molecular evaluations of mammary gland tumors in rodents were carried out. Moreover, in vitro analyses using MCF-7 and MDA-MB-231 cells were performed. The dominant metabolites present in the tested C. zeylanicum essential oil (with relative content over 1%) were cinnamaldehyde, cinnamaldehyde dimethyl acetal, cinnamyl acetate, eugenol, linalool, eucalyptol, limonene, o-cymol, and α-terpineol. The natural mixture of mentioned molecules demonstrated significant anticancer effects in our study. In the mouse model, C. zeylanicum at a higher dose (1%) significantly decreased tumor volume by 44% when compared to controls. In addition, treated tumors showed a significant dose-dependent decrease in mitotic activity index by 29% (0.1%) and 45.5% (1%) in comparison with the control group. In rats, C. zeylanicum in both doses significantly reduced the tumor incidence by 15.5% and non-significantly suppressed tumor frequency by more than 30% when compared to controls. An evaluation of the mechanism of anticancer action using valid oncological markers showed several positive changes after treatment with C. zeylanicum. Histopathological analysis of treated rat tumor specimens showed a significant decrease in the ratio of high-/low-grade carcinomas compared to controls. In treated rat carcinomas, we found caspase-3 and Bax expression increase. On the other hand, we observed a decrease in Bcl-2, Ki67, VEGF, and CD24 expressions and MDA levels. Assessment of epigenetic changes in rat tumor cells in vivo showed a significant decrease in lysine methylation status of H3K4m3 and H3K9m3 in the high-dose treated group, a dose-dependent increase in H4K16ac levels (H4K20m3 was not changed), down-regulations of miR21 and miR155 in low-dose cinnamon groups (miR22 and miR34a were not modulated), and significant reduction of the methylation status of two out of five gene promoters—ATM and TIMP3 (PITX2, RASSF1, PTEN promoters were not changed). In vitro study confirmed results of animal studies, in that the essential oil of C. zeylanicum displayed significant anticancer efficacy in MCF-7 and MDA-MB-231 cells (using MTS, BrdU, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential analyses). As a conclusion, C. zeylanicum L. showed chemopreventive and therapeutic activities in animal breast carcinoma models that were also significantly confirmed by mechanistic evaluations in vitro and in vivo.

scholarly journals Suppression of MD2 inhibits breast cancer in vitro and in vivo

2021 ◽  
Author(s):  
S. Zheng ◽  
W. Fu ◽  
R. Ma ◽  
Q. Huang ◽  
J. Gu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Normal Breast ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Breast Cells ◽  
4T1 Cells ◽  
Mcf 7

Abstract Purpose To explore the effects of the intervening measure targeting myeloid differentiation 2 (MD2) on breast cancer progression in vitro and in vivo. Methods The expression of MD2 in normal breast cells (Hs 578Bst) and three kinds of breast carcinoma cell lines (MCF-7, MDA-MB-231 s and 4T1) were detected by western blot. MTT assay was used to detect the proliferation of 4T1 cells treated by L6H21, cell migration and invasion was measured by wound healing assay and trans-well matrigel invasion assay, respectively. In addition, to further study the role of MD2 in tumor progression, we assessed the effects of inhibition of MD2 on the progression of xenograft tumors in vivo. Results The expression of MD2 is much higher in MDA-MB-231 s and 4T1cells than that in normal breast cells (Hs 578Bst) or MCF-7 cells (p < 0.05). In vitro, suppression of MD2 by L6H21 has a significant inhibition of proliferation, migration and invasion in 4T1 cells in dose-dependent manner. In vivo, L6H21 pretreatment significantly improved survival of 4T1-bearing mice (p < 0.05). Additionally, we also observed that none of the mice died from the toxic effect of 10 mg kg−1 L6H21 in 60 days. Conclusion Overall, this work indicates that suppression of MD2 shows progression inhibition in vitro and significantly prolong survival in vivo. These findings provide the potential experimental evidence for using MD2 as a therapeutic target of breast carcinoma.

scholarly journals Suppression of MD2 Inhibits Breast Cancer in Vitro and in Vivo

2021 ◽  
Author(s):  
Shurong Zheng ◽  
Weida Fu ◽  
Ruimin Ma ◽  
Qidi Huang ◽  
Junwei Gu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Normal Breast ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Breast Cells ◽  
4T1 Cells ◽  
Mcf 7

Abstract Background: To explore the effects of the intervening measure targeting myeloid differentiation 2 (MD2) on breast cancer progression in vitro and in vivo. Methods: The expression of MD2 in normal breast cells (Hs 578Bst) and three kinds of breast carcinoma cell lines (MCF-7, MDA-MB-231s and 4T1) were detected by western blot. MTT assay was used to detect the proliferation of 4T1 cells treated by L6H21, cell migration and invasion was measured by wound healing assay and transwell matrigel invasion assay, respectively. In addition, to further study the role of MD2 in tumor progression, we assessed the effects of inhibition of MD2 on the progression of xenograft tumors in vivo.Results: The expression of MD2 is much higher in MDA-MB-231s and 4T1cells than that in normal breast cells (Hs 578Bst) or MCF-7 cells (P <0.05). In vitro, suppression of MD2 by L6H21 has a significant inhibition of proliferation, migration and invasion in 4T1 cells in dose-dependent manner. In vivo, L6H21 pretreatment significanly improved survival of 4T1-bearing mice (P <0.05). Additionally, we also observed that there was none of the mice died from the toxic of 10 mg·kg−1 L6H21 in 60 days. Conclusion: Overall, this work indicates that suppression of MD2 shows progression inhibition in vitro and significantly prolong survival in vivo. These findings provide the potential experimental evidence for using MD2 as a therapeutic target of breast carcinoma.

scholarly journals Rhus coriaria L. (Sumac) Demonstrates Oncostatic Activity in the Therapeutic and Preventive Model of Breast Carcinoma

2020 ◽  
Vol 22 (1) ◽  
pp. 183 ◽  
Author(s):  
Peter Kubatka ◽  
Martin Kello ◽  
Karol Kajo ◽  
Marek Samec ◽  
Alena Liskova ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Caspase 3 ◽  
Methylation Status ◽  
Rhus Coriaria ◽  
Dose Dependent Decrease ◽  
Dose Dependent ◽  
Rat Tumor ◽  
Mcf 7

Comprehensive scientific data provide evidence that isolated phytochemicals or whole plant foods may beneficially modify carcinogenesis. The aim of this study was to evaluate the oncostatic activities of Rhus coriaria L. (sumac) using animal models (rat and mouse), and cell lines of breast carcinoma. R. coriaria (as a powder) was administered through the diet at two concentrations (low dose: 0.1% (w/w) and high dose: 1 % (w/w)) for the duration of the experiment in a syngeneic 4T1 mouse and chemically-induced rat mammary carcinoma models. After autopsy, histopathological and molecular analyses of tumor samples in rodents were performed. Moreover, in vitro analyses using MCF-7 and MDA-MB-231 cells were conducted. The dominant metabolites present in tested R. coriaria methanolic extract were glycosides of gallic acid (possible gallotannins). In the mouse model, R. coriaria at a higher dose (1%) significantly decreased tumor volume by 27% when compared to controls. In addition, treated tumors showed significant dose-dependent decrease in mitotic activity index by 36.5% and 51% in comparison with the control group. In the chemoprevention study using rats, R. coriaria at a higher dose significantly reduced the tumor incidence by 20% and in lower dose non-significantly reduced tumor frequency by 29% when compared to controls. Evaluations of the mechanism of oncostatic action using valid clinical markers demonstrated several positive alterations in rat tumor cells after the treatment with R. coriaria. In this regard, histopathological analysis of treated tumor specimens showed robust dose-dependent decrease in the ratio of high-/low-grade carcinomas by 66% and 73% compared to controls. In treated rat carcinomas, we found significant caspase-3, Bax, and Bax/Bcl-2 expression increases; on the other side, a significant down-regulation of Bcl-2, Ki67, CD24, ALDH1, and EpCam expressions and MDA levels. When compared to control specimens, evaluation of epigenetic alterations in rat tumor cells in vivo showed significant dose-dependent decrease in lysine methylation status of H3K4m3 and H3K9m3 and dose-dependent increase in lysine acetylation in H4K16ac levels (H4K20m3 was not changed) in treated groups. However, only in lower dose of sumac were significant decreases in the expression of oncogenic miR210 and increase of tumor-suppressive miR145 (miR21, miR22, and miR155 were not changed) observed. Finally, only in lower sumac dose, significant decreases in methylation status of three out of five gene promoters–ATM, PTEN, and TIMP3 (PITX2 and RASSF1 promoters were not changed). In vitro evaluations using methanolic extract of R. coriaria showed significant anticancer efficacy in MCF-7 and MDA-MB-231 cells (using Resazurin, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential analyses). In conclusion, sumac demonstrated significant oncostatic activities in rodent models of breast carcinoma that were validated by mechanistic studies in vivo and in vitro.

A Novel Triazole Derivative Drug Presenting In Vitro and In Vivo Anticancer Properties

2018 ◽  
Vol 18 (17) ◽  
pp. 1483-1493
Author(s):  
Ricardo Imbroisi Filho ◽  
Daniel T.G. Gonzaga ◽  
Thainá M. Demaria ◽  
João G.B. Leandro ◽  
Dora C.S. Costa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Hepatic Function ◽  
Anticancer Properties ◽  
Mcf 7

Background: Cancer is a major cause of death worldwide, despite many different drugs available to treat the disease. This high mortality rate is largely due to the complexity of the disease, which results from several genetic and epigenetic changes. Therefore, researchers are constantly searching for novel drugs that can target different and multiple aspects of cancer. Experimental: After a screening, we selected one novel molecule, out of ninety-four triazole derivatives, that strongly affects the viability and proliferation of the human breast cancer cell line MCF-7, with minimal effects on non-cancer cells. The drug, named DAN94, induced a dose-dependent decrease in MCF-7 cells viability, with an IC50 of 3.2 ± 0.2 µM. Additionally, DAN94 interfered with mitochondria metabolism promoting reactive oxygen species production, triggering apoptosis and arresting the cancer cells on G1/G0 phase of cell cycle, inhibiting cell proliferation. These effects are not observed when the drug was tested in the non-cancer cell line MCF10A. Using a mouse model with xenograft tumor implants, the drug preventing tumor growth presented no toxicity for the animal and without altering biochemical markers of hepatic function. Results and Conclusion: The novel drug DAN94 is selective for cancer cells, targeting the mitochondrial metabolism, which culminates in the cancer cell death. In the end, DAN94 has been shown to be a promising drug for controlling breast cancer with minimal undesirable effects.

Sign in / Sign up

Export Citation Format

Share Document