DNA Adduct Formation by the Anticancer Drug Ellipticine and Its Hydroxy Derivatives in Human Breast Adenocarcinoma MCF-7 Cells

2004 ◽  
Vol 69 (3) ◽  
pp. 603-615 ◽  
Author(s):  
Lucie Bořek-Dohalská ◽  
Eva Frei ◽  
Marie Stiborová

The cytotoxicity of the antineoplastic agent ellipticine and its 9- and 7-hydroxylated metabolites to human breast adenocarcinoma MCF-7 cells and their ability to generate DNA adducts in these cancer cells were investigated. Ellipticine and its 9-hydroxylated metabolite were found to be toxic to MCF-7 cells with IC50 values of 1.25 and 3.25 μmol l-1 for ellipticine and 9-hydroxyellipticine, respectively. In contrast, no toxicity to these cancer cells was detectable for 7-hydroxyellipticine. The nuclease P1 version of the 32P-postlabeling assay yielded a pattern of ellipticine-DNA adducts with two major and one minor adducts in MCF-7 cells, similar to the pattern of adducts detected in DNA reacted with ellipticine and the reconstituted cytochrome P450 enzyme system in vitro and in DNA in vivo. The identity of two major adducts formed in DNA of MCF-7 cells with those formed by cytochrome P450-mediated ellipticine activation in vitro was confirmed by HPLC of the isolated adducts. 9-Hydroxyellipticine was also capable of inducing DNA adducts in MCF-7 cells, but to a lesser extent. In addition, the adducts generated by 9-hydroxyellipticine were different from those generated by ellipticine. Negligible levels of DNA adducts were detectable in DNA of MCF-7 cells exposed to 7-hydroxyellipticine. The results presented here are the first report showing the formation of covalent DNA adducts with ellipticine in human breast cancer cells in culture, and suggest the formation of covalent DNA adducts as a new mode of antitumor action of ellipticine in breast cancer.

Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1565
Author(s):  
Asli Aykac ◽  
Eda Becer ◽  
Tuğçe Balcı Okcanoğlu ◽  
Meryem Güvenir ◽  
Kaya Süer ◽  
...  

Breast cancer is the most common cancer among women and in order to create alternative treatments different types of in vivo and in vitro studies have used various plant-based therapeutic agents. Humic acid (HA) induces apoptosis and has various pharmacological properties including anti-inflammatory and anti-proliferative effects. In our study, we examined the cytotoxic effects of HA at concentrations of 5, 10, 20, 50 and 100 μg/mL in human breast adenocarcinoma MCF-7 cell line for 24 and 48 h. By using MTT method, it has been found out that HA 100 g/mL had cytotoxic effect on human breast adenocarcinoma MCF-7 cell line at both 24 and 48 h; also found out that the effective dose of HA at the same time (24 and 48 h) was 50 μg/mL. The results of our study will shed light on the development of alternative therapeutic approaches in the treatment of cancer by evaluating the cytotoxic effect of HA.


2018 ◽  
Vol 16 (2) ◽  
pp. 127-137
Author(s):  
Paula Sofia Coutinho Medeiros ◽  
Ana Lúcia Marques Batista de Carvalho ◽  
Cristina Ruano ◽  
Juan Carlos Otero ◽  
Maria Paula Matos Marques

Background: The impact of the ubiquitous dietary phenolic compound p-coumaric acid on human breast cancer cells was assessed, through a multidisciplinary approach: Combined biological assays for cytotoxicity evaluation and biochemical profiling by Raman microspectroscopic analysis in cells. </P><P> Methods: Para-coumaric acid was shown to exert in vitro chemoprotective and antitumor activities, depending on the concentration and cell line probed: a significant anti-invasive ability was detected for the triple-negative MDA-MB-231 cells, while a high pro-oxidant effect was found for the estrogen- dependent MCF-7 cells. A striking cell selectivity was obtained, with a more noticeable outcome on the triple-negative MDA-MB-231 cell line. Results: The main impact on the cellular biochemical profile was verified to be on proteins and lipids, thus justifying the compound´s anti-invasive effect and chemoprotective ability. Conclusion: p-Coumaric acid was thus shown to be a promising chemoprotective/chemotherapeutic agent, particularly against the low prognosis triple-negative human breast adenocarcinoma.


Molbank ◽  
10.3390/m1083 ◽  
2019 ◽  
Vol 2019 (4) ◽  
pp. M1083
Author(s):  
Uwabagira ◽  
Sarojini

The compound 3-{[(2,3-Dichlorophenyl)amino]methyl}-5-(furan-2-ylmethylidene)-1,3-thiazolidine-2,4-dione has been designed, synthesized, and screened for its in vitro antibreast cancer activity, using human breast adenocarcinoma cell lines (MCF-7) and in vitro anti-inflammatory activity. By hemolysis assay, it showed that it has a nonhemolytic and nontoxic effect on human blood cell. The title compound 5, subjected to in vitro activities, showed that it is cytotoxic with an IC50 of 42.30 µM and a good anti-inflammatory agent. The docking results against cyclin dependent kinase 2 (CDK2) (PDB ID: 3QQK) gave insights on its inhibitory activity.


2010 ◽  
Vol 5 (12) ◽  
pp. 1934578X1000501
Author(s):  
Jiraporn Saekoo ◽  
Potchanapond Graidist ◽  
Wilairat Leeanansaksiri ◽  
Chavaboon Dechsukum ◽  
Arunporn Itharat

Dioscorealide B is a pharmacologically active compound from the rhizome of the Thai medicinal plant Dioscorea membranacea. Here, we demonstrated that in vitro treatment of dioscorealide B resulted in a cytotoxic effect on MCF-7 human breast cancer cells (IC50 = 2.82 μM). To determine whether this compound induces apoptosis in MCF-7, the Annexin V assay was performed. The data showed that the number of apoptotic cells were increased 7–12 folds over that of the control cells after treatment with various concentrations of dioscorealide B (3, 6 and 12 μM) for 24 hours. Dioscorealide B-induced apoptosis was associated with modulation of the multidomain Bcl-2 family members Bax, Bak and Bcl-2. After treatment with 3 μM dioscorealide B, acceleration of the level of proapoptotic proteins Bax and Bak were observed at 6 hours and 12 hours, respectively, while the decrease in the expression of antiapoptotic protein Bcl-2 was observed 3 hours after the treatment. These effects of dioscorealide B might result in the activation of caspase-8, -9 and -7, which lead to apoptosis in MCF-7 cells. Taken together, the results of this study provide evidence that dioscorealide B possesses an antitumor property against human breast cancer cells and thus provide the molecular basis for the further development of dioscorealide B as a novel chemotherapeutic agent for breast cancer treatment.


2020 ◽  
Vol 24 (05n07) ◽  
pp. 973-984
Author(s):  
Nthabeleng Molupe ◽  
Balaji Babu ◽  
David O. Oluwole ◽  
Earl Prinsloo ◽  
Lizhi Gai ◽  
...  

A 2,6-diiodo-3,5-dithienylvinyleneBODIPY dye was prepared and encapsulated with folate-chitosan capped Pluronic[Formula: see text] F-127 to provide drug delivery systems for photodynamic therapy (PDT). Moderately enhanced singlet oxygen quantum yields were observed for the dye encapsulation complexes in water. The in vitro dark cytotoxicity and photodynamic activity were investigated on the human breast adenocarcinoma (MCF-7) cell line. Minimal dark cytotoxicity was observed for the BODIPY dyes in 5% DMSO and when encapsulated in folate-functionalized chitosan-coated Pluronic[Formula: see text] F-127 micelles, since the cell viability values are consistently greater than 80% over the 0-40 [Formula: see text] concentration range. Upon irradiation of the samples, significant cytocidal activity was observed for the encapsulation complex of a 2,6-diiodo-8-dimethylaminophenyl-3,5-dithienylvinyleneBODIPY dye with less than 50% viable cells observed at concentrations [Formula: see text].


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