scholarly journals Synthesis and Antitumor Activity of Novel Pyridoxine-Based Bioisosteric Analogs of trans-Stilbenes

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Mikhail V. Pugachev ◽  
Thang T. N. Nguyen ◽  
Timur M. Bulatov ◽  
Roman S. Pavelyev ◽  
Alfia G. Iksanova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Anticancer Agents ◽  
Breast Cancer Cells ◽  
Wittig Reaction ◽  
Cancer Cell Line ◽  
Aromatic Aldehydes ◽  
Blue Fluorescence ◽  
Starting Point ◽  
Estrogen Receptor Negative ◽  
Mcf 7

A series of trans-6-phenylethenyl substituted pyridoxine derivatives, novel bioisosteric analogs of drugs based on trans-stilbene scaffold, were synthesized using the Wittig reaction of a bis-triphenylphosphonium pyridoxine derivative with various aromatic aldehydes. Two compounds demonstrated high activity against the estrogen-dependent MCF-7 (breast cancer) cell line with IC50 in the range of 1.9–7.9 µM and very good selectivity for other studied normal and tumor cells, including the estrogen receptor negative MDA-MB-231 breast cancer cells. The active compounds possessed an intense blue fluorescence, and this feature allowed us to effectively visualize them in cytoplasm and in nucleus. The obtained results make the described chemotype a promising starting point for the development of new anticancer agents for the therapy of estrogen-dependent malignancies.

Potential Mechanisms of miR-143/Krupple Like Factor 5 Axis in Impeding the Proliferation of Michigan Cancer Foundation-7 Breast Cancer Cell Line

2021 ◽  
Vol 11 (2) ◽  
pp. 326-332
Author(s):  
Le Ma ◽  
Zhenyu Liu ◽  
Zhimin Fan
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cell Model ◽  
Cancer Cell Line ◽  
Breast Cancer Cell Model ◽  
Underlying Mechanisms ◽  
Mcf 7

Breast cancer is one of the most prevailing cancers in females, while the cancerous heterogeneity hinders its early diagnosis and subsequent therapy. miR-143-3p is a critical mediator in malignancy development and tumorigenesis as a tumor suppressor. Its role in various tumor entities has been investigated, such as colon cancer and breast cancer. Using MCF-7 breast cancer cell model, we planned to explore the underlying mechanisms of miR-143/KLF-5 axis in retarding breast cancer cells growth. Bioinformatics analysis searched the target KLF5 of miR-143, and the miR-143-targeted mimic and inhibitor were employed to detect the changes of KLF5. After transfection of mimic miR-143, the CCK-8 reagent assessed cell proliferation. Based on optimal stimulation time, miR-143 stimulation model was established, followed by determining expression of KLF5, EGFR and PCNA via western blot and qPCR. Eventually, siRNA-KLF5 was applied to silencing KLF5 level to evaluate its role in MCF-7 cells. The transcription and translation levels of KLF5 were diminished in miR-143-mimic transfected MCF-7 cells, while enhanced in miR-143-inhibitor transfected MCF-7 cells. When MCF-7 cells were transfected with miR-143-mimic at different time points, 48 hours was found to be the optimal transfection time, with reduced transcription and translation levels of KLF5, EGFR and PCNA. The transcription and translation levels of PNCA and EGFR were declined after silencing KLF5 by siRNA. miR-143/KLF5 axis could retard the proliferation of MCF-7 breast cancer cells.

scholarly journals Interleukin-8 Promotes Epithelial-to-Mesenchymal Transition via Downregulation of Mir-200 Family in Breast Cancer Cells

2020 ◽  
Vol 19 ◽  
pp. 153303382097967
Author(s):  
Jin Zhang ◽  
Nan Shao ◽  
Xiaoyu Yang ◽  
Chuanbo Xie ◽  
Yawei Shi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Cancer Cell Line ◽  
Control Group ◽  
Mesenchymal Transition ◽  
Mcf 7

The microRNA-200 (miR-200) family has been reported to be vital for the inhibition of epithelial-to-mesenchymal transition (EMT) in tumor cells. The miR-200 family represents a complex multi-factorial regulatory network which has not been well described in breast cancer. This study aimed to clarify the underlying regulatory association between IL-8 and miR-200 family in the process of EMT in breast cancer cell. In estrogen-receptor (ER) positive breast cancer cell line MCF-7, IL-8 overexpression cells were performed by lentivirus transfection as endogenous regulation with additional exogenous IL-8 stimulation. Transient overexpressions of miR-200 family were performed after endogenous or exogenous IL-8 overexpression in MCF-7 cells. IL-8 knockdown cells were constructed via siRNA and shRNA transfection in triple negative breast cancer cell line MDA-MB-231. N-cadherin, vimentin and ZEB2 were down-regulated and E-cadherin was up-regulated in IL-8 knockdown group compared with control group. On the other hand, N-cadherin, vimentin and ZEB2 were up-regulated and E-cadherin was down-regulated in IL-8 overexpression group compared with control group. This indicated IL-8 promotes EMT in breast cancer cells. Transwell assay showed that IL-8 increased the migration and invasiveness of tumor cells. Furthermore, we performed transient overexpression of miR-200 family after endogenous or exogenous IL-8 overexpression in MCF-7 cells, which showed that the miR-200 family could inhibit EMT induced by IL-8. IL-8 promoted EMT via downregulation of miR-200 family expression in breast cancer cells and increases tumor cell migration and invasion.

scholarly journals Influence of ARHGAP29 on the Invasion of Mesenchymal-Transformed Breast Cancer Cells

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2616
Author(s):  
Katharina Kolb ◽  
Johanna Hellinger ◽  
Maike Kansy ◽  
Florian Wegwitz ◽  
Gerd Bauerschmitz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Rho Gtpase ◽  
Cancer Cell Line ◽  
Fiber Formation ◽  
Negative Regulator ◽  
Knock Down ◽  
Mesenchymal Transformation ◽  
Mcf 7

Aggressive and mesenchymal-transformed breast cancer cells show high expression levels of Rho GTPase activating protein 29 (ARHGAP29), a negative regulator of RhoA. ARHGAP29 was the only one of 32 GTPase-activating enzymes whose expression significantly increased after the induction of mesenchymal transformation in breast cancer cells. Therefore, we investigated the influence of ARHGAP29 on the invasiveness of aggressive and mesenchymal-transformed breast cancer cells. After knock-down of ARHGAP29 using siRNA, invasion of HCC1806, MCF-7-EMT, and T-47D-EMT breast cancer cells was significantly reduced. This could be explained by reduced inhibition of RhoA and a consequent increase in stress fiber formation. Proliferation of the breast cancer cell line T-47D-EMT was slightly increased by reduced expression of ARHGAP29, whereas that of HCC1806 and MCF-7-EMT significantly increased. Using interaction analyses we found that AKT1 is a possible interaction partner of ARHGAP29. Therefore, the expression of AKT1 after siRNA knock-down of ARHGAP29 was tested. Reduced ARHGAP29 expression was accompanied by significantly reduced AKT1 expression. However, the ratio of active pAKT1 to total AKT1 remained unchanged or was significantly increased after ARHGAP29 knock-down. Our results show that ARHGAP29 could be an important factor in the invasion of aggressive and mesenchymal-transformed breast cancer cells. Further research is required to fully understand the underlying mechanisms.

scholarly journals PIPERINE IN THE PREVENTION OF THE DECREASED TAMOXIFEN SENSITIVITY IN MCF-7 BREAST CANCER CELL LINE

2018 ◽  
Vol 10 (1) ◽  
pp. 335
Author(s):  
Sandy Vitria Kurniawan ◽  
Lies Sugiarti ◽  
Septelia Inawati Wanandi ◽  
Melva Louisa
Keyword(s):  
Breast Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Line ◽  
P Glycoprotein ◽  
Mcf 7 ◽  
In Cells

Objective: This study was designed to analyze the role of piperine in modulating P-glycoprotein mRNA expression when added in combination withtamoxifen to breast cancer cells in culture.Methods: MCF-7 breast cancer cells were treated with 1 μM tamoxifen with or without piperine (12.5, 25, or 50 μM) or verapamil 50 μM (P-glycoproteininhibitor positive control) for up to 12 days. We assessed the cell viability and isolated total RNA from them. We quantified P-glycoprotein expressionsusing quantitative reverse transcription polymerase chain reaction.Results: Administration of various doses of piperine decreased MCF-7 breast cancer cell viability. Piperine, when given in combination with tamoxifen,decreased the expression of P-glycoprotein mRNA in cells compared with the expression in cells treated with tamoxifen only. The effects were shownto be dose dependent.Conclusion: Piperine prevents the development of breast cancer cell tamoxifen resistance, probably through its inhibition of P-glycoprotein expression.

SYNTHESIS AND EVALUATION OF NOVEL CHEMICAL ENTITIES AS ANTI-BREAST CANCER AGENTS

INDIAN DRUGS ◽  
2019 ◽  
Vol 56 (12) ◽  
pp. 28-31
Author(s):  
D Nikam ◽  
◽  
S. Tanvar ◽  
A Kute ◽  
S Lokhande ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Cancer Cell Line ◽  
Aromatic Aldehydes ◽  
Human Breast Cancer Cell ◽  
Human Breast ◽  
Compound I ◽  
Green Method ◽  
Mcf 7

A series of dihydropyrimidone derivatives was synthesized by an efficient, simple and solvent less green method by using Beginelli reaction. Various aromatic aldehydes, urea and ethyl acetoacetate were refluxed for a few hours and the reaction monitored by periodic TLC (hexane: ethyl acetate 6:4 v/v) and products are purified by recrystallization, with characterization by FTIR, 1H NMR. All the purified compounds were subjected to evaluatation by in vitro human breast cancer cell line MDA-MB-231 and MCF-7. Compound I-k was found to be moderately active against MCF-7 with GI 50 value of -4.38.

scholarly journals Design, Synthesis and Apoptosis Inducing Activity of Non-steroidal Flavone- methanesulfonate Derivatives on MCF-7 cell line as Potential Sulfatase Inhibitor

2021 ◽  
Author(s):  
Mahdiyeh HS Javadi ◽  
Aida Iraji ◽  
maliheh safavi ◽  
Hamed Montazeri ◽  
Parastoo Tarighi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Anticancer Agents ◽  
Hydrophobic Interactions ◽  
Cancer Cell Line ◽  
Annexin V ◽  
Docking Studies ◽  
Hydrogen Bond Interaction ◽  
Cytotoxic Compound ◽  
Mcf 7

Abstract In recent years, focusing on new potent anticancer agents with selective activity is one of the greatest challenges in cancer therapy. Breast cancer is the most common cancer and the main cause of cancer deaths in women. The sulfatase enzyme plays an important role in converting the sulfated steroids into non-sulfate steroid hormones, which increases the growth and development of many hormone-dependent cancers, such as breast cancer. In this regard, structure-based optimization was conducted to design novel flavone-sulfonates pharmacophore as a new steroid sulfatase inhibitor. In the present work, the conventional methods for the synthesis of 4-oxo-2-phenyl-4H-chromen-7-yl methanesulfonate derivatives were reported. Their cytotoxicity was evaluated with MTT assay against a breast cancer cell line (MCF-7). The apoptosis inducing activity of the most cytotoxic compound 3c with an IC50 value of 0.615 µM was evaluated in comparison to docetaxel in the presence of estradiol which is a crucial growth factor to survive the cancerous cells. The results of double staining Annexin V-FITC/PI analysis suggested that the cytotoxic activity of this compound 3c in MCF-7 cells occurs via apoptosis. Molecular docking studies were conducted to clarify the inhibition mode of the most promising compound (3c) over the sulfatase (1P49) binding site. The analysis revealed the role of hydrogen bond interaction with Gly181 and hydrophobic interactions through the 1P49 active site in the ligand-receptor complex as significant descriptors to rationalize the potential inhibition activity.

scholarly journals Cytotoxic Effects of Hellebrigenin and Arenobufagin Against Human Breast Cancer Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Yu Zhang ◽  
Bo Yuan ◽  
Baolin Bian ◽  
Haiyu Zhao ◽  
Anna Kiyomi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cancer Cell Line ◽  
Therapeutic Strategies ◽  
Expression Level ◽  
Cycle Arrest ◽  
Er Positive ◽  
Mcf 7 ◽  
Positive Breast Cancer

Development of new therapeutic strategies for breast cancer is urgently needed due to the sustained emergence of drug resistance, tumor recurrence and metastasis. To gain a novel insight into therapeutic approaches to fight against breast cancer, the cytocidal effects of hellebrigenin (Helle) and arenobufagin (Areno) were investigated in human estrogen receptor (ER)-positive breast cancer cell line MCF-7 and triple-negative breast cancer cell line MDA-MB-231. Helle exhibited more potent cytotoxicity than Areno in both cancer cells, and MCF-7 cells were more susceptible to both drugs in comparison with MDA-MB-231 cells. Apoptotic-like morphological characteristics, along with the downregulation of the expression level of Bcl-2 and Bcl-xL and the upregulation of the expression level of Bad, were observed in Helle-treated MCF-7 cells. Helle also caused the activation of caspase-8, caspase-9, along with the cleavage of poly(ADP-ribose) polymerase in MCF-7 cells. Helle-mediated necrosis-like phenotype, as evidenced by the increased propidium iodide (PI)-positive cells was further observed. G2/M cell cycle arrest was also induced by Helle in the cells. Upregulation of the expression level of p21 and downregulation of the expression level of cyclin D1, cyclin E1, cdc25C and survivin were observed in MCF-7 cells treated with Helle and occurred in parallel with G2/M arrest. Autophagy was triggered in MCF-7 cells and the addition of wortmannin or 3-MA, two well-known autophagy inhibitors, slightly but significantly rescued the cells. Furthermore, similar alterations of some key molecules associated with the aforementioned biological phenomena were observed in MDA-MB-231 cells. Intriguingly, the numbers of PI-positive cells in Helle-treated MCF-7 cells were significantly reduced by wortmannin and 3-MA, respectively. In addition, Helle-triggered G2/M arrest was significantly corrected by wortmannin, suggesting autophagy induction contributed to Helle-induced cytotoxicity of breast cancer cells by modulating necrosis and cell cycle arrest. Collectively, our results suggested potential usefulness of both Helle and Areno in developing therapeutic strategies to treat patients with different types of breast cancer, especially ER-positive breast cancer.

scholarly journals Curcumin inhibits the expression of ornithine decarboxylase and adenosine deaminase genes in MCF-7 human breast cancer cells

2018 ◽  
Vol 70 (4) ◽  
pp. 639-645 ◽  
Author(s):  
Hossein Abbaspour ◽  
Afshar Safipour
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Breast Cancer Cell Line ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Cancer Cell Line ◽  
Malignant Cells ◽  
Human Breast ◽  
Dose Dependent ◽  
Mcf 7

Curcumin is the active ingredient of Curcuma longa, which inhibits the development of malignant cells. Prevention and treatment of cancer by natural compounds, especially curcumin, and understanding the mechanism of action, is an area of interest in cancer research. In this study, we evaluated the effects of curcumin on cell proliferation, ornithine decarboxylase 1 (ODC1) and adenosine deaminase (ADA) gene expression in human breast cancer cell line (MCF-7) as compared to the non-cancer line (MCF-10A). Both cell lines were subjected to increasing doses of curcumin, ranging from 0 to 30 ?g/mL. Cell viability was quantified by the MTT assay. In vitro clonogenic survival assay was performed on MCF-7 cells. Expression of ADA and ODC1 were analyzed by Western blotting and qRT-PCR. Curcumin inhibited the growth of malignant cells in a time- and dose-dependent manner. The calculated IC50 value for MCF-7 cells in 48 h was 12 ?g/mL. Forty-five to 70% decreases in colony formation were observed in MCF-7 cells treated with 30-60 ?g/mL curcumin, respectively. Our data revealed a dose-dependent downregulation of ODC1 and ADA expression and respective enzyme activities by curcumin, which correlated with decreased proliferation in the MCF-7 breast cancer cell line. These data suggest that curcumin represses the proliferation of breast cancer cells through downregulation of ODC1 and ADA gene expression, which might be another mechanism of curcumin-mediated tumor growth inhibition.

A Novel Naphthotriazolyl-4-oxoquinoline Derivative that Selectively Controls Breast Cancer Cells Survival Through the Induction of Apoptosis

2018 ◽  
Vol 18 (17) ◽  
pp. 1465-1474 ◽  
Author(s):  
Jessica R. Branco ◽  
Vanessa G. Oliveira ◽  
Amanda M. Esteves ◽  
Ingrid C. Chipoline ◽  
Miriam F.O. Lima ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Breast Cancer Cell Line ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Cancer Cell Line ◽  
Human Breast Cancer Cell ◽  
Human Breast ◽  
Mcf 7

Background: Breast cancer is a major cause of death among women worldwide. Treatment for breast cancer involves the surgical removal of cancer tissue, followed by chemotherapy. Although the treatment is efficient, especially when the cancer is detected early, recurrence is common and is often resistant to the previous treatment. Therefore, a constant search for efficient and novel drugs for the treatment of breast cancer is mandatory. Recently, triazole derivatives have shown promising effects against different types of cancer, revealing these molecules as putative anticancer drugs. Experimental: We have synthesized a series of naphthotriazolyl-4-oxoquinoline derivatives and tested their activity against a human breast cancer cell line. Among the compounds tested, we identified a molecule that killed the human breast cancer cell line MCF-7 with minimal effects on its noncancer counterpart, MCF10A. This effect was seen after 24 hours of treatment and persisted for additional 24 hours after treatment withdrawal. After 1 hour of treatment, the compound, here named 12c, promoted a decrease in cell glucose consumption and lactate production. Moreover, the cells treated with 12c for 1 hour showed diminished intracellular ATP levels with unaltered mitochondrial potential and increased reactive oxygen species production. Additionally, apoptosis was triggered after treatment with the drug for 1 hour. All of these effects are only observed with MCF-7 cells, and not MCF10A. These data show that 12c has selective activity against breast cancer cells and is a potential candidate for a novel anticancer drug. Results and Conclusion: The naphthotriazolyl-4-oxoquinoline derivatives were obtained in good to moderate yields, and one of them, 12c, exhibited strong and selective antitumor properties. The antitumor mechanism involves inhibition of glycolysis, diminished intracellular ATP levels, induction of ROS production and triggering of apoptosis. These effects are all selective for cancer cells, since noncancer cells are unaffected, and these effects can only be attributed to the whole molecule, as different pharmacophoric groups did not reproduce these effects.

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