Design, Synthesis and Cytotoxicity Evaluation of New 3, 5-Disubstituted-2-Thioxoimidazolidinones

2018 ◽  
Vol 18 (4) ◽  
pp. 573-582 ◽  
Author(s):  
Khaled R.A. Abdellatif ◽  
Mostafa M. Elbadawi ◽  
Mohammed T. Elsaady ◽  
Amer A. Abd El-Hafeez ◽  
Takashi Fujimura ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Topoisomerase I ◽  
Cancer Cell Line ◽  
Cytotoxic Agents ◽  
Dependent Manner ◽  
Human Lung Fibroblast ◽  
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Background: Some 2-thioxoimidazolidinones have been reported as anti-prostate and anti-breast cancer agents through their inhibitory activity on topoisomerase I that is considered as a potential chemotherapeutic target. Objective: A new series of 3,5-disubstituted-2-thioxoimidazolidinone derivatives 10a-f and their S-methyl analogs 11a-f were designed, synthesized and evaluated for cytotoxicity against human prostate cancer cell line (PC-3), human breast cancer cell line (MCF-7) and non-cancerous human lung fibroblast cell line (WI-38). </P><P> Results and Method: While compounds 10a-f showed a broad range of activities against PC-3 and MCF-7 cell lines (IC50 = 34.0 – 186.9 and 24.6 – 147.5 µM respectively), the S-methyl analogs 11a-f showed (IC50 = 22.7 – 198.5 and 16.9 – 188.2 µM respectively) in comparison with 5-fluorouracil (IC50 = 60.7 and 40.7 µM respectively). 11c (IC50 = 22.7 and 29.2 µM) and 11f (IC50 = 28.7 and 16.9 µM) were the most potent among all compounds against both PC-3 and MCF-7 respectively with no cytotoxicity against WI-38. Conclusion: The newly synthesized compounds showed good activity against PC-3 and MCF-7 cell lines in comparison with 5-fluorouracil. Compounds 11c and 11f bound with human topoisomerase I similar to its known inhibitors and significantly inhibited its DNA relaxation activity in a dose dependent manner which may rationalize their molecular mechanism as cytotoxic agents.

scholarly journals Anticancer activity of chicken cathelicidin peptides against different types of cancer

2021 ◽  
Author(s):  
Maged Mostafa Mahmoud ◽  
Ahmed M. Al-Hejin ◽  
Turki S. Abujamel ◽  
Modhi Alenezi ◽  
Fadwa Aljoud ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Line ◽  
Cancer Cell Line ◽  
High Dose ◽  
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Abstract This study served as the pioneer in studying the anti-cancer role of chicken cathelicidin peptides. Chicken cathelicidins were used as anticancer agent against the breast cancer cell line (MCF-7) and human colon cancer cell line (HCT116). An in vivo investigation was also achieved to evaluate the role of chicken cathelicidin in Ehrlich ascites cell (EAC) suppression as a tumor model after subcutaneous implantation in mice. In addition, the mechanism of action of the interaction of cationic peptides with breast cancer cell line MCF-7 was also investigated. It was found during the study that exposure of cell lines to higher concentration of chicken cathelicidin for 72 h reduced cell lines growth rate by 90%-95%. These peptides demonstrated down-regulation of (cyclin A1 and cyclin D genes) which are essential for G1/S phase transient and S/G2 phase and consequently causes “prometaphase arrest” ultimately leading to death of MCF-7 cells. The study showed two- and three-times higher expression of the caspase-3, and − 7 genes respectively in MCF-7 cells treated with chicken peptides (especially cathelicidin-2 and − 3) relative to untreated cells which encouraged pro-apoptotic pathway, autophagy, and augmentation of the anti-proliferative activity. Our data showed that chicken ( CATH-1 ) enhance releasing of TNFα, INF-γ and upregulation of granzyme K in treated mice groups, in parallel, the tumor size and volume was reduced in the treated EAC-bearing groups after cathelicidin administration compared to untreated EAC-bearing group. Additionally, animals received high dose of cathelicidin-1 (40 µg/ml) displayed an apical survival rate compared to untreated carcinoma control and animals which received low dose of cathelicidin (10 and 20 µg/ml). Tumor of mice groups treated with chicken cathelicidin displayed high area of necrosis compared to untreated EAC-bearing mice. Based on histological analysis and immunohistochemical staining revealed that the tumor section in Ehrlich solid tumor exhibited a strong Bcl2 expression in untreated control compared to mice treated with 10 & 20 µg/ml of cathelicidin. Interestingly, low expression of Bcl2 were observed in mice taken 40 µg/ml of CATH-1. This study drive intention in treatment of cancer through the efficacy of anticancer efficacy of chicken cathelicidin peptides.

scholarly journals An Antioxidant Polysaccharide from Ganoderma lucidum Induces Apoptotic Activity in Breast Cancer Cell Line 

2022 ◽  
Author(s):  
Md. Moyen Uddin Pk ◽  
Rumana Pervin ◽  
Mohammad Shahangir Biswas ◽  
Matiar Rahman
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Line ◽  
Ganoderma Lucidum ◽  
Cancer Cell Line ◽  
Dependent Manner ◽  
Apoptotic Activity ◽  
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The purpose of this study is to elucidate the apoptotic activity of Ganoderma lucidum  polysaccharide (GLP) in a human breast cancer cell line MCF-7 in vitro.  According to DPPH assay, GLP showed a good antioxidant (IC 50  value is 202.4 µg/mL). Based on MTT assay, the results showed that GLP inhibits MCF-7 cells proliferation in a dose- and time- dependent manner (p<0.001). IC 50   values of the cytotoxicity of GLP and doxorubin  were 110.907 µg/mL and 58.206 µg/mL respectively. The results from the flow cytometry indicated that GLP could induce apoptotic activity through inducing the up-regulation of the Bax and Caspase-9 and the down-regulation of the BcL-2 in MCF-7 cells. At 2×IC 50 , GLP increased the early-apoptotic and dead cells of MCF-7 from 18.23% to 34.76% and 8.45% to16.34% respectively. In conclusion, the GLP shows anticancer activity against MCF-7 through preventing the proliferation and inducing the apoptosis of MCF-7 cells. Our data provide the potential molecular targets in cancer prevention and reveal the key barriers in the current anticancer drugs development.

scholarly journals Synthesis and Evaluation of New Brominated Azaflavones and Azaflavanone Derivatives as Cytotoxic agents against Breast Cancer Cell Line (MCF-7)

2019 ◽  
Vol 53 (1) ◽  
pp. 117-126 ◽  
Author(s):  
Srujana Muthadi ◽  
Baswaraju Macha ◽  
Prashanthi Mamidi ◽  
Sravanthi Manchinella ◽  
Achaiah Garlapati ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Line ◽  
Cancer Cell Line ◽  
Cytotoxic Agents ◽  
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scholarly journals Evaluation of Cytotoxicity Effects of Combination Nano-Curcumin and Berberine in Breast Cancer Cell Line

2018 ◽  
Vol 12 (4) ◽  
pp. 47-50
Author(s):  
Parisa ZiaSarabi ◽  
◽  
AmirReza Hesari ◽  
Malihe Bagheri ◽  
Maryam Baazm ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Line ◽  
Cancer Cell Line ◽  
Cytotoxicity Test ◽  
Dependent Manner ◽  
Cytotoxicity Effects ◽  
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Background: Berberine and Nano-curcumin are two herbal medicines with strong anti-cancer effects on tumor cells, but low toxicity on normal cells, when used alone. Breast cancer is known as the most common cancer in women and second deadly one. In this study, we evaluated the cytotoxicity effects of combination Berberine and Nano-curcumin in breast cancer cell line to see whether they have further synergism cytotoxicity on MCF-7 breast cancer cell line. Methods: The cytotoxicity effects of Berberine and Nano-curcumin alone and in combination, were evaluated in MCF-7 cell lines using MTT cytotoxicity test. Statistical analysis is done through one-way ANOVA and Tukey multiple range tests. Results: Analyzing results of this study showed that cytotoxicity of Nano-curcumin was higher than Berberine in a dose-dependent manner. The IC50 of combination Berberine and Nano-curcumin was lower and showed higher cytotoxicity in MCF-7 cells compared with the time we use each of these drugs alone. Conclusion: In this study co-treatment of Berberine and Nano-curcumin significantly inhibited the growth of MCF-7 breast cancer cell line and resulted in synergism cytotoxicity effects. These results indicated on their potency to further combination of these two drugs with other agents and common chemotherapies to improve breast cancer outcomes.

scholarly journals Antioxidant Activity and Antiproliferative Effects of Lycium barbarum’s (Goji berry) Fractions on Breast Cancer Cell Lines

Folia Medica ◽  
2019 ◽  
Vol 61 (1) ◽  
pp. 104-112 ◽  
Author(s):  
Kaloyan D. Georgiev ◽  
Iliya J. Slavov ◽  
Ivan A. Iliev
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Line ◽  
Free Fraction ◽  
Lycium Barbarum ◽  
Polysaccharide Fraction ◽  
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Abstract Background: Lycium barbarum has gained immense popularity over the past decade because of its antioxidant properties. There are many reports of observed health benefits of juice consumption, including prophylaxis in neoplastic disease and treatment of tumors. Materials and methods: In this study, we isolated three fractions of Lycium barbarum fruits – total water, pectin-free and polysaccharide, and determined their antioxidant activity by ORAC and HORAC assays. We investigated the antiproliferative effects of Lycium barbarum’s pectin-free and polysaccharide fraction on three different breast cell lines - MCF-10A (non-tumorigenic epithelial breast cell line), MCF-7 (breast cancer cell line, estrogen, progesterone receptors +, HER2-), and MDA-MB-231 (breast cancer cell line, triple negative), by the MTT dye reduction assay. Results: The Lycium barbarum’s pectin-free fraction showed concentration-dependent growth inhibition on the three cell lines, moreover, on cancer cells (MCF- 7 and MDA-MB-231) it was significantly more pronounced. The polysaccharide fraction showed negligible activity on the three cell lines, only the highest concentration (1000 μg/mL), suppressed the proliferation of MCF-7 cells. The combination of pectin-free and polysaccharide fraction on MCF-7 did not show the expected synergistic effect. Conclusion: We found a relative correlation between the polyphenolic content of the extracts and the observed effects. The pectin-free extract had the highest content of polyphenols with the best antioxidant and antineoplastic activity against breast cancer cells. Addition of polysaccharide to the pectin-free fraction contributes to its pharmacological activity.

Comparison of the effects of nobiletin and letrozole on the activity and expression of aromatase in the MCF-7 breast cancer cell line

2017 ◽  
Vol 95 (4) ◽  
pp. 468-473 ◽  
Author(s):  
Seyedeh Tayebeh Rahideh ◽  
Mohammad Keramatipour ◽  
Mitra Nourbakhsh ◽  
Fariba Koohdani ◽  
Mostafa Hoseini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Viability ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Line ◽  
Cancer Cell Line ◽  
Dependent Manner ◽  
Mtt Assays ◽  
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Nobiletin (NOB) is one of the polymethoxyflavones mainly found in citrus fruits. Aromatase or cytochrome P450 (CYP19) enzyme catalyzes the last and rate-limiting step in estrogen biosynthesis. This study was carried out to investigate the effect of NOB on the activity and expression of aromatase, and to compare this property with letrozole (LET) as aromatase inhibitor in the MCF-7 breast cancer cell line. Cell viability was assessed with 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assays. Aromatase enzyme activity based on the conversion of androgenic substrate testosterone into 17β-estradiol was determined. CYP19 gene expression was measured by quantitative real-time PCR. MTT assays demonstrated that NOB at a concentration of 100 μmol/L decreased cell viability in a time-dependent manner (P < 0.05). NOB significantly inhibited aromatase at the concentration of 0.1 μmol/L (P = 0.013), whereas other concentrations had no effect. Treatment with 10 μmol/L and 1 μmol/L of NOB for 48 h significantly increased (P = 0.001) and decreased (P = 0.02) relative aromatase expression, respectively. The combination of LET and NOB had no effect on aromatase. This study showed for the first time that NOB decreases the activity and expression of aromatase at low concentrations in MCF-7 breast cancer cells.

scholarly journals Gynura procumbens Prevents Chemoresistance through Inhibition MDR1 Expression on MCF-7 Breast Cancer Cell Line and Sensitizes the Cells to Doxorubicin

2015 ◽  
Vol 17 (1) ◽  
pp. 51 ◽  
Author(s):  
Nunuk Aries Nurulita ◽  
Edy Meiyanto ◽  
Eishou Matsuda ◽  
Masashi Kawaichi
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Line ◽  
Cell Model ◽  
Cancer Cell Line ◽  
Dependent Manner ◽  
Mdr1 Expression ◽  
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The long-term exposure of doxorubicin (Dox) causes enhancement in MDR1 expression that leads tobreast cancer cell resistance. This protein become a serious problem in cancer treatment and also well-knownas negative prognostic factor in breast cancer malignancies. The new approach using natural chemopreventivesubstance was developed to inhibit this resistance progress. This study was aimed to investigate whether ethylacetate fraction of Gynura procumnens (FEG) can prevent chemoresistance through suppressing the MDR1 proteinexpression. MCF-7 cell was used as chemoresistance cell model. The MCF-7 cells were maintained with 100nM Dox-contained medium for five weeks. The chemoprevention effect of FEG was investigated by treatedMCF-7/Dox with sub-toxic concentration of FEG. The cytotoxic properties of MCF-7 cells were determinedusing MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay. Immunofluorescenceand western blotting analysis was performed to detect the MDR1 expression. MCF-7/Dox cells need higherconcentration for inhibiting cell growth, were compared with MCF-7, shown by IC50value. The MDR1 proteinlevel elevated after Dox exposure in time dependent manner. The FEG treatment decreased MDR-1 proteinlevel with dose dependent manner. FEG in combination with DOX potentiates the DOX effect on breast cancercell growth inhibition. The FEG prevents the chemoresistance development in breast cancer cell line, MCF-7induced by Dox through inhibiting MDR1 expression. The additional of FEG enhances Dox effect on cell deathinduction. Thus, FEG could be developed as co-chemotherapy agent for reverse multidrug resistance

Activation of Intrinsic Apoptosis and G1 Cell Cycle Arrest by a Triazole Precursor, N-(4-chlorophenyl)-2-(4-(3,4,5-trimethoxybenzyloxy)benzoyl)-hydrazinecarbothioamide in Breast Cancer Cell Line

2020 ◽  
Vol 20 (9) ◽  
pp. 1072-1086
Author(s):  
Stephanie B. Arulnathan ◽  
Kok H. Leong ◽  
Azhar Ariffin ◽  
Huda S. Kareem ◽  
Kevin K.H. Cheah
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Line ◽  
Cycle Arrest ◽  
Flow Cytometric ◽  
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Background: Oxadiazoles, triazoles, and their respective precursors have been shown to exhibit various pharmacological properties, namely antitumour activities. Cytotoxic activity was reported for these compounds in various cancer cell lines. Aim and Objectives: In this study, we aim at investigating the mechanism of apoptosis by N-(4-chlorophenyl)-2-(4- (3,4,5-trimethoxybenzyloxy)benzoyl)-hydrazinecarbothioamide, a triazole precursor, henceforth termed compound P7a, in breast cancer cell line, MCF-7. We first screen a series of analogues containing (3,4,5-trimethoxybenzyloxy) phenyl moiety in breast cancer cell lines (MCF-7 and MDA-MB-231) to select the most cytotoxic compound and demonstrate a dose- and time-dependent cytotoxicity. Then, we unravel the mechanism of apoptosis of P7a in MCF-7 as well as its ability to cause cell cycle arrest. Methods: Synthesis was performed as previously described by Kareem and co-workers. Cytotoxicity of analogues containing (3,4,5-trimethoxybenzyloxy)phenyl moiety against MCF-7 and MDA-MB-231 cell lines was evaluated using the MTS assay. Flow cytometric analyses was done using Annexin V/PI staining, JC-1 staining and ROS assay. The activity of caspases using a chemoluminescence assay and western blot analysis was conducted to study the apoptotic pathway induced by the compound in MCF-7 cells. Lastly, cell cycle analysis was conducted using flow cytometry. Results: Upon 48 hours of treatment, compound P7a inhibited the proliferation of human breast cancer cells with IC50 values of 178.92 ± 12.51μM and 33.75 ± 1.20μM for MDA-MB-231 and MCF-7, respectively. Additionally, compound P7a showed selectivity towards the cancer cell line, MCF-7 compared to the normal breast cell line, hTERT-HME1, an advantage against current anticancer drugs (tamoxifen and vinblastine). Flow cytometric analyses using different assays indicated that compound P7a significantly increased the proportion of apoptotic cells, increased mitochondria membrane permeabilisation and caused generation of ROS in MCF-7. In addition, cell cycle analysis showed that cell proliferation was arrested at the G1 phase in the MCF-7 cell line. Furthermore, upon treatment, the MCF-7 cell line showed increased activity of caspase-3/7, and caspase-9. Lastly, the western blot analysis showed the up-regulation of pro-apoptotic proteins along with up-regulation of caspase-7 and caspase-9, indicating that an intrinsic pathway of apoptosis was induced. Conclusion: The results suggest that compound P7a could be a potential chemotherapeutic agent for breast cancer.

scholarly journals Antioxidant, anticancer and molecular docking activity of tulsi plant

2018 ◽  
Author(s):  
C.M. Noorjahan ◽  
T. Saranya
Keyword(s):  
Breast Cancer ◽  
Vero Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Line ◽  
Ocimum Sanctum ◽  
Human Breast ◽  
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An investigation was carried out to study the antioxidant, anticancer and docking activities of medicinal plant, Tulsi – Ocimum sanctum. The results of antioxidant activity of Tulsi leaves extract showed that tulsi leaves has good free radical scavenging ability and IC50 value was found to be 54.23% at 500 µg/ml. The results of anticancer activity of Ocimum santum on normal VERO cell and MCF-7 cell line has showed good anticancer activity having the IC50 concentration at 51.1 ì|g/ml against MCF-7 cell lines – Human Breast cancer cell line thereby indicating that the percentage of cell viability increases with the increased concentration of Ocimum santum (Tulsi) whereas 24.4% cell viability was recorded in the normal VERO cell line. DNA laddering assay was performed on agarose gel electrophoresis. A clear fragmented DNA ladders were observed in tulsi treated MCF-7– Human Breast cancer cell lines. But the untreated normal VERO cell lines did not show any DNA fragmentation. Thereby confirms that Ocimum sanctum induced cell death on breast cancer cell line MCF-7 cancerous cell through apoptosis. Molecular docking was carried out (AutoDock tools), Docking simulations was performed using Lamarckian genetic algorithm of Solis and Wests local search method. Interaction between HDAC6 and Cirsilileon possessing binding energy showed +15.91kcal for interaction studies. It was found that most of the hydrogen bonding is with the residues TYR 76, TRP 35, SER 67, TYR 81, GLU 33, TYR 48, ILE 69 and MET 53 present in the binding pocket. The ligand was docked with the target protein, and the best docking poses were identified and the binding poses of the cirsilieon was shown. This act as the best docking poses shows how the ligand molecule fits into the binding region of the target protein.

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