Synthesis and Apoptotic Activities of New 2(3H)-benzoxazolone Derivatives in Breast Cancer Cells

2020 ◽  
Vol 21 (1) ◽  
pp. 84-90
Author(s):  
Emine Erdag ◽  
Eda Becer ◽  
Yusuf Mulazim ◽  
Hafize Seda Vatansever ◽  
Hilal Kabadayı ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cytochrome C ◽  
Caspase 3 ◽  
Biological Activities ◽  
Cancer Cell Line ◽  
Mannich Bases ◽  
Control Group ◽  
Anti Cancer ◽  
Fas L ◽  
Mcf 7

Background: 2(3H)-Benzoxazolone derivatives are preferential structural blocks in pharmacological probe designing with the possibility of modifications at various positions on the core structure. Benzoxazolones showed various biological activities such as analgesics, anti-inflammatory and anti-cancer. Objective: In the present work, we have prepared new Mannich bases of 2(3H)-benzoxazolone derivatives and evaluated their cytotoxicities and proapoptotic properties in MCF-7 breast cancer cell line. Methods: The structures of these compounds were characterized by FT-IR, elemental analysis, 1H and 13C NMR. Cytotoxicities of all the target compounds were investigated by MTT assay. Apoptotic properties of compounds were evaluated by immunocytochemistry using antibodies against caspase-3, cytochrome-c, FasL, and also TUNEL assay. Results: These two novel compounds, 1 and 2, both have the same piperazine substituent on the nitrogen atom of benzoxazolone and the main difference in the structures of these compounds is the presence of Cl substituent at the 5- position of the benzoxazolone ring. MTT results showed that compounds 1 and 2 were effective in terms of reduction of cell viability at 100μM and 50μM concentration for 48h, respectively. As a result of immunohistochemical staining, Fas L and caspase-3 immunoreactivities were significantly increased in MCF-7 cells after treatment with compound 1. Additionally, caspase-3 and cytochrome-c immunoreactivities were also increased significantly in MCF-7 cells after treatment with compound 2. The number of TUNEL positive cells was significantly higher in MCF-7 cells when compared with the control group after treatment with both compounds 1 and 2. Conclusion: It could be concluded that N-substituted benzoxazolone derivatives increase potential anti-cancer effects and they could be promising novel therapeutic agents for chemotherapy.

scholarly journals Regulation of Chloride Intracellular Channel Protein 1 and Caspase -3 mRNA Expression by Hydroethanolic Extract of Aegle marmelos Fruit Human Breast Cancer Cell Line-MCF-7

2021 ◽  
pp. 586-593
Author(s):  
S. Dhivya ◽  
R. Gayatri Devi ◽  
J. Selvaraj ◽  
A. Jothi Priya
Keyword(s):  
Breast Cancer ◽  
Caspase 3 ◽  
Cancer Cell Line ◽  
Human Breast ◽  
Rt Pcr ◽  
Aegle Marmelos ◽  
Hydroethanolic Extract ◽  
The Given ◽  
Intracellular Channel ◽  
Mcf 7

Introduction: Cancer is the second leading cause of death all over the world where among all types of cancer breast cancer is said to be the leading cancer followed by lung cancer. The aim of this study is to find the regulation of chloride intracellular channel protein 1 and caspase -3 mRNA expression by hydroethanolic extract of Aegle marmelos fruit human breast cancer cell line-MCF-7. Materials and methods: MCF-7 cells were collected from NCCS Pune, India. It is stored in Dubecos Modified Eagle's Medium. The Aegle marmelos fruit was collected from the herbal department and its extract was prepared. The extract of Aegle marmelosis used in treating MCF-7 cells at different dosages in in vitro.  Isolation of total RNA from MCF-7 cells. The cells will be mixed with total RNA isolation reagent, sonicated and RNA will be isolated as per the standard method. c-DNA conversion and real time polymerase chain reaction. The c-DNA will be synthesized using reverse transcription by commercially available (RT-PCR) kit. Two microlitres of c-DNA will be used for amplification of clic-1 and caspase-3 using gene specific primers by commercially available RT-PCR kit (SyBr kit) and comparative CT method will be used to see the expression of genes. Untreated MCF-7 cells were compared with MCF-7 cells treated with various concentrations of the extract (10, 20 and 40ug). The statistical data’s were collected from the SPSS software version 21. Result: The given extract inhibits the proliferation of MCF-7 cells therefore said to have antiproliferative activity. Different doses of extract were tested (200ug-500ug) out of which 400ug of extract were preferred. Conclusion: The given plant extract has anti proliferative properties and hence can be used as a drug to treat breast cancer.

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.

Design and Synthesis of Novel Thiosemicarbazones as Potent Anti-breast Cancer Agents

2019 ◽  
Vol 16 (4) ◽  
pp. 446-452 ◽  
Author(s):  
Mashooq Ahmad Bhat ◽  
M. Al-Tahhan ◽  
Mohamed A. Al-Omar ◽  
Ahmed M. Naglah ◽  
Abdullah Al-Dhfyan
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Side Population ◽  
Biological Activities ◽  
Cancer Cell Line ◽  
Inhibition Assay ◽  
Reference Drug ◽  
Design And Synthesis ◽  
Pure Compounds ◽  
Mcf 7

Background: Thiosemicarbazones and its derivatives received a great pharmaceutical importance due to their prominent biological activities. Methods: A series of disubstituted thiosemicarbazone derivatives (1-12) were designed and synthesized as pure compounds in good yield. All the synthesized compounds were analyzed by spectral data. The anticancer activity of all the compounds was performed against breast cancer MCF-7 and MDA-MB-231 cell lines. Results: Most of the compounds showed activity against breast cancer MCF-7 and MDA-MB-231 cell lines with (IC50 = 12.25 µM ‒ 185.35 µM) and (IC50 = 12.97 µM ‒ 107.33 µM), respectively. Compound 9 presented (IC50 = 12.76 µM and 12.97 µM) against MCF-7 and MDA-MB-231 cell lines, respectively. Conclusion: Compound 9, was found to exhibit significant anti-breast cancer activity. This compound was further evaluated for side population percent inhibition assay on the breast cancer cell line MCF-7 at 5 and 10 µM concentration. It showed superiority to block side population by more than 80% at 5 μM concentration compared to the reference drug verapamil.

scholarly journals Metformin suppresses the proliferation and invasion through NF-kB and MMPs in MCF-7 cell line

2019 ◽  
Vol 45 (3) ◽  
pp. 295-304
Author(s):  
Nail Besli ◽  
Guven Yenmis ◽  
Matem Tunçdemir ◽  
Elif Yaprak Sarac ◽  
Sibel Doğan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Line ◽  
Cancer Cell Line ◽  
Immunocytochemical Staining ◽  
Breast Adenocarcinoma ◽  
Control Group ◽  
Expression Levels ◽  
Er Positive ◽  
Mcf 7

AbstractObjectiveMCF-7 cells, a breast cancer cell line, are used for experiments of estrogen receptor (ER)-positive breast cancer and many sub-clones representing different classes of ER-positive tumors. We aimed to determine the efficacy of metformin, a potential anti-cancer agent, on the cell proliferation, and the expressions of NF-kB (p65), MMP-2 and MMP-9 in MCF-7 cell line.Materials and methodsMCF-7 cells (human breast adenocarcinoma) were treated with elevating doses of metformin (0–50 mM) for 24 h. The anti-proliferative effect of metformin was studied by BrdU proliferation assay, and the expression levels of NF-kB (p65), MMP-2 and MMP-9 were analyzed by immunocytochemical staining.ResultsThe percentage of cell proliferation was reduced significantly by 10 and 50 mM doses of metformin (p < 0.001). The expression levels of nuclear NF-kB (p65), MMP-9 and MMP-2 were considerably reduced in 50 mM metformin treated cells while the expression of cytoplasmic NF-kB (p65) elevated compared to control group (p < 0.05). Ten millimolar metformin also reduced expression of MMP-9 significantly (p < 0.05).ConclusionMetformin may act on the proliferation, and the processes of invasion and metastasis of MCF-7 cells through blocking NF-kB, which is intensely expressed in breast cancer cells, and through diminishing the expression of MMP-2 and MMP-9 significantly.

Evaluation of Anti-Tumor Potential of Lactobacillus acidophilus ATCC4356 Culture Supernatants in MCF-7 Breast Cancer

2020 ◽  
Vol 21 ◽  
Author(s):  
Ramazan Behzadi ◽  
Ahmad Hormati ◽  
Karim Eivaziatashbeik ◽  
Sajjad Ahmadpour ◽  
Fatemeh Khodadust ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Nude Mice ◽  
Control Group ◽  
Bacterial Strains ◽  
Anti Cancer ◽  
99Mtc Mibi ◽  
Culture Supernatants ◽  
Mcf 7

Background: Anti-cancer activity of some lactic acid bacterial strains is well documented in several literatures. Lactobacillus strains have received considerable attention as a beneficial microbiota. The aim of this study is to evaluate the effects of anti-tumor activities of L. acidophilus ATCC4356 culture supernatants on the MCF-7 human breast cancer cells. Materials and methods: Anti-cancer effect of 24h and 48h culture supernatants at various concentrations (1.25, 2.5, 5, 10 and 20 µg/ml) were determined by various in vitro and in vivo assays including MTT, tumor volume measurement as well as 99mTc-MIBI biodistribution in MCF-7 tumor bearing nude mice and histopathology test. For evaluation of the related mechanism of action, quantitative PCR was conducted. Results: The 48h culture supernatants at 10 and 20 µg/ml exhibited significant in vitro inhibition of MCF-7 cell proliferation. However, this inhibition was not observed for HUVEC human endothelial normal cells. Q-PCR indicated that treatment by the supernatant led to a significant downregulation of VEGFR ( ̴ 0.009 fold) and Bcl-2 ( ̴ 0.5 fold) and upregulation of p53 ( ̴ 1.3 fold). In vivo study using MCF-7 xenograft mouse models demonstrated reduction in tumor weight and volume by both 24h and 48h supernatants (10 µg/ml and 20 µg/ml) after 15 days. According to the 99mTc-MIBI biodistribution result, treatment of MCF-7 bearing nude mice with both 24h and 48h supernatant (20 µg/ml) led to significant decrease in tumor uptake compared with the control group. Conclusion: These results suggest that the culture supernatants of L. acidophilus ATCC4356 at suitable concentrations can be considered as a good alternative nutraceutical with promising therapeutic indexes for breast cancer.

Effects of Michigan Cancer Foundation-7/A New Adriamycin Cell-Derived Exosomes on MCF-7 Cell Apoptosis and Drug Sensitivity Through Ubiquitin Carboxyl-Terminal Hydrolase L1

2020 ◽  
Vol 10 (12) ◽  
pp. 1780-1785
Author(s):  
Chen Li ◽  
Yu Wang ◽  
Na Xu ◽  
Xin Liu
Keyword(s):  
Breast Cancer ◽  
Cell Apoptosis ◽  
Drug Sensitivity ◽  
Mrna Level ◽  
Cancer Cell Line ◽  
Normal Breast ◽  
Control Group ◽  
Experiment Control ◽  
Size And Morphology ◽  
Mcf 7

Exosomes secreted by adriamycin-resistant human breast cancer cell line MCF-7/ADR can promote the resistance of normal breast cancer cells. However, the exosomes? contents remain unclear. This article investigated the effect of UCHL1 in MCF-7/ADR-derived exosomes on MCF-7 cell apoptosis and drug sensitivity. In this experiment, control group (NC group), Exosome group, Exosome+ siRNA-UCHL1 group were set followed by analysis of exosomes morphology by electron microscope, UCHL1 and Tubulin level by Western Blot, UCHL1 level by immunofluorescence, UCHL1 mRNA level by qRT-PCR, cell apoptosis by flow cytometry, and drug sensitivity by MTT assay. The size and morphology of exosomes were normal with high expression of UCHL1 and CD63. Compared to NC group, UCHL1 level in Exosome group was significantly increased, while siRNAUCHL1 could reduce UCHL1 level; in addition, Exosome group showed significantly decreased cell apoptosis (P < 0.01) which was elevated in Exosome+siRNA-UCHL1 group (P < 0.05); finally, drug sensitivity in Exosome group was significantly increased (P < 0.01) and decreased in the Exosome+siRNA-UCHL1 group (P < 0.05). MCF-7/ADR-derived UCHL1 in exosome can increase UCHL1 level in MCF-7 cells, reduce cell apoptosis and drug sensitivity of cells.

scholarly journals Biological activities of synthetic coumarin derivatives

2016 ◽  
Author(s):  
◽  
Kabange Kasumbwe
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Caspase 3 ◽  
Morphological Changes ◽  
Annexin V ◽  
Positive Control ◽  
Inflammatory Activity ◽  
Anti Cancer ◽  
Anti Inflammatory ◽  
Mcf 7

Coumarins are naturally occurring α-benzopyrone derivatives known for their pharmacological properties such as anticoagulant, antimicrobial, anticancer, antioxidant, anti-inflammatory and antiviral properties. The pharmacological, biochemical, and curative applications of coumarins depend on the substitution around the coumarin core structure. In the present study, seven halogenated coumarins CMRN1 - CMRN7 were synthesized and evaluated for mosquito larvicidal, repellancy , and insecticidal activity against Anopheles arabiensis. Furthermore, the antimicrobial properties of compounds CMRN1 - CMRN7 were evaluated by assessing the bacterial and fungicidal activities using the disc diffusion method. The anti-inflammatory properties were evaluated using the 5-lipoxygenase kit assay. The evaluation of the safe use of the compounds was determined using the Brine shrimp lethal test. The potential carcinogenic properties of the studied compounds was done using the Salmonella mutagenicity test. The anti-cancer property of the studied compounds was evaluated against UACC62 (Melanoma), MCF-7 (Breast cancer), and PBMC (Peripheral blood mononuclear) cell lines using of MTT assay. The apoptotic potential of the synthesized coumarin was evaluated against UACC62 (Melanoma) cell by assessing their morphological changes, membrane change, mitochondria membrane potential, and caspase-3 activity using the Annexin V-PI staining, JC-1, caspase-3 enzyme kits, respectively, on flow cytometer. The results were compared to a known anti-cancer drug, doxorubicin. The results showed that compounds CMRN1, CMRN2, CMRN4, CMRN5 and CMRN7 exerted 100% larval mortality within 24 h of exposure. All halogenated coumarins reversibly knocked down adult mosquitoes but did not kill them after 24 h of exposure. Furthermore, the adulticidal activity of the compounds was considered only mild to moderate. The antimicrobial activity of the synthetized coumarins CMRN1 - CMRN7 were assessed against E. coli, K. pneumoniae, S. marcescens, S. faecalis, B. cereus, B. coagulans, B. stearothermophilus, C. freundii, S. aureus and M. luteus bacteria and three yeast cultures, C. albicans, C. utilis, S. cerevisiae as well as two fungal species, A. flavus and A. niger. Compounds CMRN1 and CMRN2 showed bacterial growth inhibition for all the tested species except K. pneumonia and B. stearothermophilus. Compounds CMRN4 and CMRN7 showed moderate bacterial inhibition against B. cereus, M. luteus and S. aureus. The anti-inflammatory activity of the coumarins analogues showed that 1 mg/mL of the compounds CMRN1, CMRN2, CMRN4 and CMRN5 displayed moderate anti-inflammatory activity when compared to the positive control, 15-lapoxygenase. The cytotoxicity results of the studied synthetized coumarins displayed selective activity towards the cancer cell lines used in this study. Our studies showed that CMRN1, CMRN2, CMRN4, and CMRN5 had significant cytotoxity effect against UACC-62 (Melanoma) and MCF-7 ( Breast) cancer cells with an inhibitory concentration (IC50) which displayed significant cytotoxicity effect, in particular CMRN4 and CMRN5. These compounds CMRN1- CMRN7 showed no toxicity effect against PBMCs cell line. The mechanism of cell death, that is, necrosis or apoptosis induced by the coumarins was investigated against UACC-62 (Melanoma). We found that CMRN1, CMRN2, CMRN4, CMRN5 induced morphological changes, characteristic of apoptosis . Annexin V kit showed that CMRN1, CMRN2 and CMRN5 showed early apopotosis and late apoptosis was particularly higher for compound CMRN4. The disruption of the mitochondria membrane was noticed to be greater in CMRN1 and CMRN5 when compared to the positive control doxorubicin. Compound CMRN4 produced high levels of caspase-3 positive compared to the control. The coumarin compounds showed no mutagenicity and were also found to be non-toxic to brine shrimps. In conclusion, compounds CMRN1, CMRN2, CMRN4, CMRN5 and CMRN7 are potential larvicidal agents because they exhibited close to 100% activity within 24 h. Furthermore, the anti-cancer efficiency of compounds CMRN1, CMRN2, CMRN4, and CMRN5, is enough qualification for them to be optimized for increase anticancer potency.

scholarly journals The Effect of Micro RNA-34a and carboplatin combination on the inducing apoptosis of Breast Cancer Cell line

2021 ◽  
Author(s):  
Sajjad Eslamkhah ◽  
Nazila Alizadeh ◽  
Sahar Safaei ◽  
Mohammad Amini ◽  
ahad Mokhtarzadeh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cell Line ◽  
Caspase 3 ◽  
Cancer Cell Line ◽  
Micro Rna ◽  
Control Group ◽  
Expression Levels ◽  
Micro Rnas

Abstract Aim: Breast cancer (BC) has been classified among the main causes of death owing to females' cancer. Carboplatin is a platinum-based chemotherapeutic drug that is an important treatment option for BC. But high and frequent doses of carboplatin usually reducing the reaction of cancer cells to medication. There is an immediate need to establish methods for increasing the carboplatin susceptibility to BC cells. For instance, micro RNAs (miRNAs) such as MiR34a demonstrate significant potential. Considering that, this research was planned to explore the better clinical effect and underlying mechanism of miR-34a as a possible tumor inhibitor and drug resistance regulator in compound with carboplatin chemotherapy drug in the cell lines of BC in humans. Methods: MCF-7 cell line was transfected with miR-34a to perform functional analyses. Subsequently, the MTT assay was applied to assess cell viability. Cell viability and cell death associated gene expression amounts including Bax, Bcl-2, caspase-3, MDR1, P53, and mir34-a, were examined through real-time quantitative PCR. Results: Findings showed that miR-34a upregulation significantly decreased MCF7 cell viability in comparison with control group. Furthermore, separate treatment of cells with miR-34a mimics and carboplatin could significantly increase Bax, Caspase-3, P53, and decrease in Bcl-2 mRNA expression levels evaluated to the non-treated group. Moreover, by reduction in expression levels of the MDR1 gene, BC cells' reaction to carboplatin has increased via miR-34a. Conclusion: In line with the findings, it could be inferred that miR-34a may improve the responsiveness of breast cancer cells to carboplatin chemotherapy with downregulation of MDR1.

scholarly journals Niclosamide loaded biodegradable chitosan nanocargoes: an in vitro study for potential application in cancer therapy

2017 ◽  
Vol 4 (11) ◽  
pp. 170611 ◽  
Author(s):  
Saba Naqvi ◽  
Shanid Mohiyuddin ◽  
P. Gopinath
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Chitosan Nanoparticles ◽  
Cancer Cell Line ◽  
Human Lung Cancer ◽  
Anti Cancer ◽  
Mcf 7

Chitosan nanoparticles can advance the pharmacological and therapeutic properties of chemotherapeutic agents by controlling release rates and targeted delivery process, which eliminates the limitations of conventional anti-cancer therapies and they are also safe as well as cost-effective. The aim of present study is to explore the anti-tumour effect of niclosamide in lung and breast cancer cell lines using biocompatible and biodegradable carrier where nanoparticles loaded with hydrophobic drug (niclosamide) were synthesized, characterized and applied as a stable anti-cancer agent. Niclosamide loaded chitosan nanoparticles (Nic-Chi Np's) of size approximately 100–120 nm in diameter containing hydrophobic anti-cancer drug, i.e. niclosamide, were prepared. Physico-chemical characterization confirms that the prepared nanoparticles are spherical, monodispersed and stable in aqueous systems. The therapeutic efficacy of Nic-Chi Np's was evaluated against breast cancer cell line (MCF-7) and human lung cancer cell line (A549). MTT assay reveals the cell viability of the prepared Nic-Chi Np's against A549 and MCF-7 cells and obtained an IC 50 value of 8.75 µM and 7.5 µM, respectively. Acridine orange/ethidium bromide dual staining results verified the loss of the majority of the cells by apoptosis. Flow cytometer analysis quantified the generation of intracellular reactive oxygen species (ROS) and signified that exposure to a higher concentration (2 × IC 50 ) of Nic-Chi Np's resulted in elevated ROS generation. Notably, Nic-Chi Np treatment showed more apoptosis and cell death in MCF-7 as compared to A549. Further, the remarkable induction of apoptosis by Nic-Chi Np's was confirmed by semi-quantitative reverse transcription polymerase chain reaction, scanning electron microscopy and cell-cycle analysis. Thus, Nic-Chi Np's may have a great potential even at low concentration for anti-cancer therapy and may replace or substitute more toxic anti-mitotic drugs in the near future.

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