scholarly journals Design and Synthesis of Newly Synthesized Acrylamide Derivatives as Potential Chemotherapeutic Agents against MCF-7 Breast Cancer Cell Line Lodged on PEGylated Bilosomal Nano-Vesicles for Improving Cytotoxic Activity

2021 ◽  
Vol 14 (10) ◽  
pp. 1021
Author(s):  
Islam Zaki ◽  
Reham A. I. Abou-Elkhair ◽  
Ali H. Abu Almaaty ◽  
Ola A. Abu Ali ◽  
Eman Fayad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bile Salt ◽  
Cytotoxic Activity ◽  
Cell Line ◽  
Chemotherapeutic Agents ◽  
Multi Drug Resistance ◽  
Dna Flow Cytometry ◽  
Tubulin Polymerization ◽  
Β Tubulin ◽  
Mcf 7

Cancer is a multifaceted disease. With the development of multi drug resistance, the need for the arousal of novel targets in order to avoid these drawbacks increased. A new series of acrylamide derivatives was synthesized from starting material 4-(furan-2-ylmethylene)-2-(3,4,5-trimethoxyphenyl)oxazol-5(4H)–one (1), and they are evaluated for their inhibitory activity against β-tubulin polymerization. The target molecules 2–5 d were screened for their cytotoxic activity against breast cancer MCF-7 cell line. The results of cytotoxicity screening revealed that compounds 4e and 5d showed good cytotoxic profile against MCF-7 cells. Compounds 4e produced significant reduction in cellular tubulin with excellent β-tubulin polymerization inhibition activity. In addition, compound 4e exhibited cytotoxic activity against MCF-7 cells by cell cycle arrest at pre-G1 and G2/M phases, as shown by DNA flow cytometry assay. Aiming to enhance the limited aqueous solubility and, hence, poor oral bioavailability of the prepared lead acrylamide molecule, 4e-charged PEGylated bilosomes were successfully fabricated via thin film hydration techniques as an attempt to improve these pitfalls. Twenty-three full factorial designs were manipulated to examine the influence of formulation variables: types of bile salt including either sodium deoxy cholate (SDC) or sodium tauro cholate (STC), amount of bile salt (15 mg or 30 mg) and amount of DSPE–mPEG-2000 amount (25 mg or 50 mg) on the characteristics of the nanosystem. The F7 formula of entrapment efficiency (E.E% = 100 ± 5.6%), particle size (PS = 280.3 ± 15.4 nm) and zeta potential (ZP = −22.5 ± 3.4 mv) was picked as an optimum formula with a desirability value of 0.868. Moreover, prominent enhancement was observed at the compound’s cytotoxic activity (IC50 = 0.75 ± 0.03 µM) instead of (IC50 = 2.11 ± 0.19 µM) for the unformulated 4e after being included in the nano-PEGylated bilosomal system.

scholarly journals A Combination of an Antimitotic and a Bromodomain 4 Inhibitor Synergistically Inhibits the Metastatic MDA-MB-231 Breast Cancer Cell Line

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Thandi Mqoco ◽  
André Stander ◽  
Anna-Mart Engelbrecht ◽  
Anna M Joubert
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Chemotherapeutic Agents ◽  
Breast Cancer Cell Lines ◽  
Mcf 7

Current chemotherapeutic agents have many side effects and are toxic to normal cells, providing impetus to identify agents that can effectively eliminate tumorigenic cells without damaging healthy cells. The aim of this study was to examine whether combining a novel BRD4 inhibitor, ITH-47, with the antimitotic estradiol analogue, ESE-15-ol, would have a synergistic effect on inhibiting the growth of two different breast cancer cell lines in vitro. Our docking and molecular dynamics studies showed that compared to JQ1, ITH-47 showed a similar binding mode with hydrogen bonds forming between the ligand nitrogens of the pyrazole, ASN99, and water of the BRD4 protein. Data from cell growth studies revealed that the GI50 of ITH-47 and ESE-15-ol after 48 hours of exposure was determined to be 15 μM and 70 nM, respectively, in metastatic MDA-MB-231 breast cancer cells. In tumorigenic MCF-7 breast cancer cells, the GI50 of ITH-47 and ESE-15-ol was 75 μM and 60 nM, respectively, after 48 hours of exposure. Furthermore, the combination of 7.5 μM and 14 nM of ITH-47 and ESE-15-ol, respectively, resulted in 50% growth inhibition of MDA-MB-231 cells resulting in a synergistic combination index (CI) of 0.7. Flow cytometry studies revealed that, compared to the control, combination-treated MDA-MB-231 cells had significantly more cells present in the sub-G1 phase and the combination treatment induced apoptosis in the MDA-MB-231 cells. Compared to vehicle-treated cells, the combination-treated cells showed decreased levels of the BRD4, as well as c-Myc protein after 48 hours of exposure. In combination, the selective BRD4 inhibitor, ITH-47, and ESE-15-ol synergistically inhibited the growth of MDA-MB-231 breast cancer cells, but not of the MCF-7 cell line. This study provides evidence that resistance to BRD4 inhibitors may be overcome by combining inhibitors with other compounds, which may have treatment potential for hormone-independent breast cancers.

Structural and In Vitro Biological Studies of Organotin(IV) Precursors; Selective Inhibitory Activity Against Human Breast Cancer Cells, Positive to Estrogen Receptors

2012 ◽  
Vol 65 (12) ◽  
pp. 1625 ◽  
Author(s):  
Vasilis I. Balas ◽  
Christina N. Banti ◽  
Nikolaos Kourkoumelis ◽  
Sotiris K. Hadjikakou ◽  
George D. Geromichalos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
Cancer Cells ◽  
Cell Line ◽  
Breast Cancer Cells ◽  
X Ray ◽  
Er Positive ◽  
Normal Human ◽  
Mcf 7

Crystals of Ph3SnCl (1) were grown from a methanol/acetonitrile solution. Compounds [Ph3SnOH]n (2) and [(Ph2Sn)4Cl2O2(OH)2] (3) were crystallized from diethyl ether/methanol/acetonitrile and hot acetone/water solutions respectively, of the white precipitation, formed by adding KOH to solutions of 1 and [Ph2SnCl2] in 1 : 1 and 1 : 2 molar ratios respectively. Complex 1 was characterized by X-ray crystallography. X-ray structure determination of compounds 2 and 3 confirmed the previously reported identities. The molecular structure of 1, reported here, is a new polymorphic form of the known one for Ph3SnCl. Four independent [Ph3SnCl] molecules constitute the crystal structure of 1. The moieties are packed in two pairs in a tail-to-tail arrangement. Complexes 1–3 were evaluated for their in vitro cytotoxic activity (cell viability) against human cancer cell lines: HeLa (human cervical), MCF-7 (breast, estrogen receptor (ER) positive), MDA-MB-231 (breast, ER negative), A549 (lung), Caki-1 (kidney carcinoma), 786-O (renal adenocarcinoma), K1 (thyroid carcinoma), and the normal human lung cell line MRC-5 (normal human fetal lung fibroblast cells) versus, the normal immortalized human mammary gland epithelial cell line MTSV17 with a sulforhodamine B (SRB) assay. The results show potent cytotoxic activity of the complexes against all cell lines used, which was superior to that of cisplatin (CDDP). Compounds 1–3 showed higher activity against breast cancer cells MCF-7 (ER positive) than against of MDA-MB-231 (ER negative). These findings prompted us to search for possible interaction of these complexes with other cellular elements of fundamental importance in cell proliferation. The influence of these complexes 1–3 upon the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX), as well as their binding affinity towards calf thymus-DNA, were kinetically and theoretically studied.

scholarly journals 3-Vinylazetidin-2-Ones: Synthesis, Antiproliferative and Tubulin Destabilizing Activity in MCF-7 and MDA-MB-231 Breast Cancer Cells

2019 ◽  
Vol 12 (2) ◽  
pp. 56 ◽  
Author(s):  
Wang ◽  
Malebari ◽  
Greene ◽  
O’Boyle ◽  
Fayne ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Docking Simulation ◽  
Chemotherapeutic Agents ◽  
Mitotic Catastrophe ◽  
Phase Cell ◽  
Tubulin Polymerization ◽  
Mcf 7

Microtubule-targeted drugs are essential chemotherapeutic agents for various types of cancer. A series of 3-vinyl-β-lactams (2-azetidinones) were designed, synthesized and evaluated as potential tubulin polymerization inhibitors, and for their antiproliferative effects in breast cancer cells. These compounds showed potent activity in MCF-7 breast cancer cells with an IC50 value of 8 nM for compound 7s 4-[3-Hydroxy-4-methoxyphenyl]-1-(3,4,5-trimethoxyphenyl)-3-vinylazetidin-2-one) which was comparable to the activity of Combretastatin A-4. Compound 7s had minimal cytotoxicity against both non-tumorigenic HEK-293T cells and murine mammary epithelial cells. The compounds inhibited the polymerisation of tubulin in vitro with an 8.7-fold reduction in tubulin polymerization at 10 M for compound 7s and were shown to interact at the colchicine-binding site on tubulin, resulting in significant G2/M phase cell cycle arrest. Immunofluorescence staining of MCF-7 cells confirmed that β-lactam 7s is targeting tubulin and resulted in mitotic catastrophe. A docking simulation indicated potential binding conformations for the 3-vinyl-β-lactam 7s in the colchicine domain of tubulin. These compounds are promising candidates for development as antiproiferative microtubule-disrupting agents.

scholarly journals CYTOTOXIC ACTIVITY OF ALKALOID EXTRACTS OF DIFFERENT PLANTS AGAINST BREAST CANCER CELL LINE

2017 ◽  
Vol 10 (7) ◽  
pp. 168
Author(s):  
Farah A Al-marzook ◽  
Rabab Omran
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Breast Cancer Cell Line ◽  
Total Alkaloid ◽  
Cancer Cell Line ◽  
Total Alkaloids ◽  
Alkaloid Extracts ◽  
Mcf 7

Objectives: To study in vitro cytotoxic activity of total alkaloid extracts of Pinus sabiniana L., Phoenix dactylifera L. and Ferocactus sp. L. against breast cancer cell line Michigan Cancer Foundation-7 (MCF-7) and non-tumorigenic fetal hepatic cell line (WRL-68). Methods: Plant powder of each P. sabiniana L. leaves, P. dactylifera L. pollen grains, and Ferocactus sp. L. The leaves were extracted separately with 80% methanol, chloroform at pH 2 and pH 10 and the chloroform portion was dried to obtain the total alkaloid extracts. The total alkaloids were detected qualitatively by Mayer’s, Dragendorff’s and Hager’s reagents and estimated quantitatively by bromocresol green spectrophotometry depending on the atropine calibration curve. The cytotoxic activity was evaluated by 3-[4, 5-dimethylthiazoyl]-2, 5-diphenyltetrazolium bromide assay. Results: The extract of P. sabiniana L. had highest total alkaloid content (164.62±2.8 mg/100 g dry weight of plant) than the other plants (P. dactylifera l., Ferocactus sp. L.), the total alkaloids of Ferocactus sp. L. and P. dactylifera L., reduced the cell viability of both cell lines, the highest reduction occurred in the concentration 400 μg/ml was 46±2.20% (MCF-7) and 56.2±2.2% (WRL-68) for Ferocactus sp. L., followed by 56.2±2.2% (MCF-7) and 57.5±3.2% (WRL-68) for P. dactylifera L. The alkaloids of P. sabiniana was very lower effects on both cell lines MCF-7, and WRL-68 was 89.3±3.44% and 90.16±2.7%, respectively, at the same concentration. Conclusion: Plant alkaloids had variable effects against cancer and normal cell lines depending on the type of alkaloid compounds and their concentration in the extract.

scholarly journals CYTOTOXIC ACTIVITY OF ALKALOIDS EXTRACTED FROM THREE IRAQI PLANTS AGAINST BREAST CANCER CELL LINE

2017 ◽  
Vol 10 (9) ◽  
pp. 78 ◽  
Author(s):  
Farah A Al-marzook ◽  
Rabab Omran
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Line ◽  
Total Alkaloid ◽  
Cancer Cell Line ◽  
Total Alkaloids ◽  
Mcf 7

  Objectives: Screening for cytotoxic activity of total alkaloid extracts of Eucalyptus camaldulensis, Aloe vera, and Capparis spinosa against breast cancer cell line Michigan Cancer Foundation-7 (MCF-7) and nontumorigenic fetal hepatic cell line (WRL-68).Methods: The plant powders were extracted separately with 80% methanol and chloroform at pH 2 and 10. Total alkaloids were detected qualitatively by Mayer’s, Dragendorff’s, and Hager‘s reagents and estimated quantitatively by bromocresol green spectrophotometry depending on the atropine calibration curve. The cytotoxic activity was evaluated by 3-[4, 5-dimethylthiazoyl]-2, 5-diphenyltetrazolium bromide assay.Results: The extract of E. camaldulensis had highest total alkaloid content (24.50±1.70 mg/100 g plant dry weight) than the others. The total alkaloids (400 μg/ml) of E. camaldulensis reduced the cell viability of both cell lines MCF-7 and WRL-68 to 45.25±2.20% and 92.00±1.55%, respectively, and the inhibitory concentration 50% of cells were 375.50 μg/ml for MCF-7. The alkaloids of C. spinosa had effect 79.80±7.08% and 89.50±0.09% against MCF-7and WRL-68, respectively. While the total alkaloids of A. vera had slightly effect on both cell lines.Conclusion: Plant alkaloids appeared variable cytotoxic activity against cancer and normal cell lines depending on the alkaloid contents, concentrations, purity, and cell line types.

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