scholarly journals Design, Synthesis, and Evaluation of Novel 2-Methoxyestradiol Derivatives as Apoptotic Inducers through an Intrinsic Apoptosis Pathway

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 123
Author(s):  
Li-Xin Sheng ◽  
Jiang-Yu Zhang ◽  
Li Li ◽  
Xiao Xie ◽  
Xiao-An Wen ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Cell Lines ◽  
Proliferative Activity ◽  
Inhibitory Concentration ◽  
Dependent Manner ◽  
Human Breast ◽  
Apoptosis Pathway ◽  
Single Access ◽  
Intrinsic Apoptosis Pathway ◽  
Mcf 7

In order to discover novel derivatives in the anti-tumor field, reported anti-tumor pharmacophores (uridine, uracil, and thymine) were combined with 2-methoxyestradiol, which has been characterized as having excellent biological properties in terms of anti-tumor activity. Thus, 20 hybrids were synthesized through etherification at the 17β-OH or 3-phenolic hydroxyl group of 2-methoxyestradiol, and evaluated for their biological activities against the human breast adenocarcinoma MCF-7 cell lines, human breast cancer MDA-MB-231 cell lines, and the normal human liver L-O2 cell lines. As a result, all the uridine derivatives and single-access derivatives of uracil/thymine possessed good anti-proliferative activity against tested tumor cells (half maximal inhibitory concentration values from 3.89 to 19.32 µM), while only one dual-access derivative (21b) of thymine possessed good anti-proliferative activity (half maximal inhibitory concentration ≈ 25 µM). Among them, the uridine derivative 11 and the single-access derivative of uracil 12a possessed good anti-proliferative selectivity against tested tumor cells. Furthermore, basic mechanism studies revealed that hybrids 11 and 12a could induce apoptosis in MCF-7 cells through mitochondrial pathway. These hybrids induced morphological changes in MCF-7 cells, causing mitochondrial depolarization. These two hybrids also had the following effects: arrest of the cell cycle at the G2 phase; up regulation of Apaf-1, Bax, and cytochrome c; down regulation of Bcl-2 and Bcl-xL for both mRNA and protein; and increase of the expression for caspase-8 and -9. Finally, apoptotic effector caspase-3 was increased, which eventually caused nuclear apoptosis at least through an intrinsic pathway in the mitochondria. Additionally, hybrids 11 and 12a could specifically bind to estradiol receptor alpha in a dose-dependent manner.

In Vitro and In Silico Determination of some N-ferrocenylmethylaniline Derivatives as Anti-Proliferative Agents against MCF-7 Human Breast Cancer Cell Lines

2021 ◽  
Vol 21 ◽  
Author(s):  
Nadjiba Zegheb ◽  
Cherifa Boubekri ◽  
Touhami Lanez ◽  
Elhafnaoui Lanez ◽  
Tuba Tüylü Küçükkılınç ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Proliferative Activity ◽  
Human Breast Cancer ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Ferrocene Derivatives ◽  
Mcf 7

Background: Since the binding of estradiol to its receptor promotes breast cancer cell proliferation (in the ER+ tumours), many molecules targeting this protein have been synthesized to counteract the estradiol action. Ferrocene derivatives have proved their efficiency against hormone-dependent breast cancer cells (MCF-7). Objective: In this study, we aimed to find new ferrocene derivatives having pharmacochemistry properties as potential drugs against human breast cancer cells. Methods: A series of 29 N-ferrocenylmethylaniline derivatives A0-A28 were synthesised, and their anti-proliferative activity against both hormone-dependent (MCF-7) and independent (MDA-MB 231) human breast cancer cell lines were performed using the MTT test. Molecular docking and drug-likeness prediction were also performed for the five most active derivatives towards MCF-7. A QSAR model was also developed for the perdition of the anti-proliferative activity against MCF-7 cell lines using molecular descriptors and MLR analysis. Results: All studied derivatives demonstrated better cytotoxicity against MCF-7 compared to the MDA-MB-231 cell lines, and compounds A2, A9, A14, A17, and A27 were the most potent ones; however, but still less active than the standard anti-cancer drug crizotinib. The QSAR study revealed good predictive ability as shown by R2cv = 0.848. Conclusion: In vitro and in silico results indicated that derivatives A2, A9, A14, A17, and A27 possess the highest anti-proliferative activity, t. These results can be used to design more potent N-ferrocenylmethylaniline derivatives as anti-proliferative agents.

scholarly journals Induction of Apoptosis by Gluconasturtiin-Isothiocyanate (GNST-ITC) in Human Hepatocarcinoma HepG2 Cells and Human Breast Adenocarcinoma MCF-7 Cells

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1240
Author(s):  
Asvinidevi Arumugam ◽  
Muhammad Din Ibrahim ◽  
Saie Brindha Kntayya ◽  
Nooraini Mohd Ain ◽  
Renato Iori ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Cell Lines ◽  
Chromatin Condensation ◽  
Time Dependent ◽  
Breast Adenocarcinoma ◽  
Dependent Manner ◽  
Human Breast ◽  
Human Breast Adenocarcinoma ◽  
Mcf 7

Gluconasturtiin, a glucosinolate present in watercress, is hydrolysed by myrosinase to form gluconasturtiin-isothiocyanate (GNST-ITC), which has potential chemopreventive effects; however, the underlying mechanisms of action have not been explored, mainly in human cell lines. The purpose of the study is to evaluate the cytotoxicity of GNST-ITC and to further assess its potential to induce apoptosis. GNST-ITC inhibited cell proliferation in both human hepatocarcinoma (HepG2) and human breast adenocarcinoma (MCF-7) cells with IC50 values of 7.83 µM and 5.02 µM, respectively. Morphological changes as a result of GNST-ITC-induced apoptosis showed chromatin condensation, nuclear fragmentation, and membrane blebbing. Additionally, Annexin V assay showed proportion of cells in early and late apoptosis upon exposure to GNST-ITC in a time-dependent manner. To delineate the mechanism of apoptosis, cell cycle arrest and expression of caspases were studied. GNST-ITC induced a time-dependent G2/M phase arrest, with reduction of 82% and 93% in HepG2 and MCF-7 cell lines, respectively. The same treatment also led to the subsequent expression of caspase-3/7 and -9 in both cells demonstrating mitochondrial-associated cell death. Collectively, these results reveal that GNST-ITC can inhibit cell proliferation and can induce cell death in HepG2 and MCF-7 cancer cells via apoptosis, highlighting its potential development as an anticancer agent.

scholarly journals Anti-proliferative Activity and Apoptotic Potential of Britannin, a Sesquiterpene Lactone from Inula aucheriana

2012 ◽  
Vol 7 (8) ◽  
pp. 1934578X1200700 ◽  
Author(s):  
Maryam Hamzeloo Moghadam ◽  
Homa Hajimehdipoor ◽  
Soodabeh Saeidnia ◽  
Azadeh Atoofi ◽  
Roxana Shahrestani ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Sesquiterpene Lactone ◽  
Cell Lines ◽  
Mtt Assay ◽  
Proliferative Activity ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Breast Adenocarcinoma ◽  
Human Breast ◽  
Human Breast Adenocarcinoma ◽  
Mcf 7

Inula aucheriana n-hexane, CHCl3 and MeOH extracts were evaluated for their anti-proliferative activity against HepG-2, MCF-7, MDBK and A-549 cells. The CHCl3 extract exhibited cytotoxic activity to the above cell lines with IC50 values of 13.5, 23.4, 10.5, and 26.9 μg/mL, respectively. The sesquiterpene lactone britannin was isolated from the above extract. This was further evaluated in the MTT assay to demonstrate strong cytotoxicity to the mentioned cell lines (IC50: 2.2, 5.9, 5.4, and 3.5 μg/mL, respectively), and the apoptotic inducing properties of britannin were evaluated on human breast adenocarcinoma (MCF-7) cells through the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.

scholarly journals Zeaxanthin Induces Apoptosis in Human Uveal Melanoma Cells through Bcl-2 Family Proteins and Intrinsic Apoptosis Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Ming-Chao Bi ◽  
Richard Rosen ◽  
Ren-Yuan Zha ◽  
Steven A. McCormick ◽  
E. Song ◽  
...  
Keyword(s):  
Cell Lines ◽  
Uveal Melanoma ◽  
Colorimetric Assay ◽  
Retinal Pigment ◽  
Melanoma Cells ◽  
Retinal Pigment Epithelial Cells ◽  
Dependent Manner ◽  
Apoptosis Pathway ◽  
Intrinsic Apoptosis Pathway ◽  
Induced Apoptosis

The cytotoxic effects of zeaxanthin on two human uveal melanoma cell lines (SP6.5 and C918) and related signaling pathways were studied and compared to effects on normal ocular cells (uveal melanocytes, retinal pigment epithelial cells, and scleral fibroblasts). MTT assay revealed that zeaxanthin reduced the cell viability of melanoma cells in a dose-dependent manner (10, 30, and 100 μM), with IC50at 40.8 and 28.7 μM in SP6.5 and C918 cell lines, respectively. Zeaxanthin did not affect the viability of normal ocular cells even at the highest levels tested (300 μM), suggesting that zeaxanthin has a selectively cytotoxic effect on melanoma cells. Zeaxanthin induced apoptosis in melanoma cells as indicated by annexin V and ethidium III flow cytometry. Western blot analysis demonstrated that zeaxanthin decreased the expression of antiapoptotic proteins (Bcl-2 and Bcl-xL) and increased the expression of proapoptotic proteins (Bak and Bax) in zeaxanthin-treated melanoma cells. Zeaxanthin increased mitochondrial permeability as determined by JC-1 fluorescein study. Zeaxanthin also increased the level of cytosol cytochrome c and caspase-9 and -3 activities, but not caspase-8, as measured by ELISA assay or colorimetric assay. All of these findings indicate that the intrinsic (mitochondrial) pathway is involved in zeaxanthin-induced apoptosis in uveal melanoma cells.

On the Cytotoxicity of Chiral Ruthenium Complexes Containing Sulfur Amino Acids Against Breast Tumor Cells (MDA-231 and MCF-7)

2020 ◽  
Vol 20 ◽  
Author(s):  
Celisnolia M. Leite ◽  
João Honorato de Araujo-Neto ◽  
Rodrigo S. Corrêa ◽  
Legna Colina-Vegas ◽  
Diego Martínez-Otero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Amino Acids ◽  
Tumor Cells ◽  
Cell Lines ◽  
Breast Tumor ◽  
Human Breast Cancer ◽  
Ruthenium Complexes ◽  
Sulfur Amino Acids ◽  
Human Breast ◽  
Mcf 7

Background: Breast cancer is one of the most common types among women. Its incidence progressively increases with age, especially after age 50. Platinum compounds are not efficient in the treatment of breast cancer, highlighting the use of other metals for the development of new chemotherapeutic agents. Objective: This paper aims to obtain three new ruthenium compounds that incorporate sulfur amino acids in their structures and to investigate their cytotoxic activity in breast tumor cell lines. Methods: Complexes with general formula [Ru(AA)(dppb)(bipy)] (complexes 1 and 2) or [Ru(AA)(dppb)(bipy)]PF6 (complex 3), where AA = L-cysteinate (1), D-penicillaminate (2), and L-deoxyalliinate (3), dppb = 1,4- bis(diphenylphosphino)butane and 2,2´-bipyridine, were obtained from the cis-[RuCl2(dppb)(bipy)] precursor. The cytotoxicity of the complexes on MDA-MB-231 (triple negative human breast cancer); MCF-7 (double positive human breast cancer) and V79 (hamster lung fibroblast) were performed by the MTT (4,5-dimethylthiazol-2-yl-2,5- diphenyltetrazolium bromide) method. The control agent was the cisplatin, which is a commercially available drug for cancer treatment. Results: In complexes (1) and (2), the ligands are coordinated to the metal center by nitrogen and sulfur atoms, while in complex (3) coordination is through the oxygen and nitrogen atoms. These suggestions are based on the infrared and 31P1H NMR data. For complexes (1) and (2), their X-ray structures were determined confirming this suggestion. The three complexes are stable in a mixture of DMSO (80 %) and biological medium (20 %) for at least 48 h and presented cytotoxicity against the MDA-MB-231 and MCF-7 tumor cells with reasonable selectivity indexes. Conclusion: Our work demonstrated that ruthenium complexes containing sulfur amino acids, bipyridines and bisphosphines showed cytotoxicity against the MDA-MB-231 and MCF-7 cancer cell lines, in vitro, and that they interact weakly with the DNA (Deoxyribonucleic Acid) and the HSA (Human Serum Albumin) biomolecules.

scholarly journals Introducing a novel chemotherapeutic drug formulated by Anthraflavic acid for the treatment of human breast carcinoma and Type 2 diabetes mellitus

2021 ◽  
Author(s):  
Gang Zhao ◽  
Arunachalam Chinnathambi ◽  
Tahani Awad Alahmadi ◽  
Milton Wainwright
Keyword(s):  
Breast Carcinoma ◽  
Cell Lines ◽  
Cancer Cell ◽  
Biological Activities ◽  
Cancer Cell Lines ◽  
Human Breast Carcinoma ◽  
Alpha Amylase ◽  
Dependent Manner ◽  
Human Breast ◽  
Mcf 7

IntroductionMolecular docking as a versatile theoretical method was used to investigate the biological activities of anthraflavic acid in the presence of alpha amylase. The outcomes revealed that anthraflavic acid has a considerable binding affinity to the enzyme with a docking score of -7.913 kcal/mol.Material and methodsThese outcomes were further evaluated with free binding energy calculations, and it was concluded that anthraflavic acid could be a potential inhibitor for alpha amylase. The as Anthraflavic acid was explored in the anti-human breast carcinoma tests. The in vitro cytotoxic and anti-breast carcinoma effects of biologically synthesized Anthraflavic acid against MCF-7, CAMA-1, SK-BR-3, MDA-MB-231, AU565 [AU-565], and Hs 281.T cancer cell lines were assessed.ResultsThe anti-breast carcinoma properties of the Anthraflavic acid could significantly remove MCF-7, CAMA-1, SK-BR-3, MDA-MB-231, AU565 [AU-565], and Hs 281.T cancer cell lines in a time and concentration-dependent manner by MTT assay.ConclusionsThe IC50 of the Anthraflavic acid were 159, 193, 253, 156, 241, and 218 µg/mL against MCF-7, CAMA-1, SK-BR-3, MDA-MB-231, AU565 [AU-565], and Hs 281.T cancer cell lines. It seems that the anti-human breast carcinoma effect of recent nanoparticles is due to their antioxidant effects.After clinical study, Anthraflavic acid can be utilized as an efficient drug in the treatment of breast carcinoma in humans.

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