Preclinical evaluation of PARP inhibition in breast cancer: Comparative effectiveness of olaparib and iniparib.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1042-1042 ◽  
Author(s):  
Maura B. Cotter ◽  
Aisling Pierce ◽  
Patricia M. McGowan ◽  
Louise Flanagan ◽  
Cecily Quinn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Staining Intensity ◽  
Cancer Cell Lines ◽  
Parp Inhibition ◽  
Breast Cancer Cell Lines ◽  
Main Function ◽  
Dependent Manner

1042 Background: The main function of PARP1 is repair of single-strand DNA. Phase I/II clinical trials have shown that the PARP inhibitor, olaparib has efficacy in BRCA1/2-related breast cancer. Due to the similarities between BRCA1/2-associated and triple negative breast cancer (TNBC), we hypothesise that TNBC may also be sensitive to PARP inhibition. In order to assess this we addressed the effects of 2 PARP/PARP-like inhibitors, on a panel of breast cancer cell lines. Methods: PARP1 was measured by immunohistochemistry in 101 TNBC and 116 non-TN cancers. Comparative growth inhibitory capacity of olaparib and iniparib was evaluated using cell viability (MTT) and colony formation assays in 12 breast cancer cell lines (TN=7, non-TN=5). Results: Using immunohistochemistry, PARP1 staining was predominantly nuclear with some cytoplasmic staining. High staining intensity for PARP1 was found more frequently in ER-negative (p = 0.001), in high grade (p = 0.013) and in Ki67-positive ( p = 0.003) samples. Potentially important was the finding that high PARP1 staining intensity was detected more frequently in TN than non-TN samples (p = 0.0001). IC50 concentrations across 12 cell lines ranged from 3.7-31 µM for olaparib and 13-70 µM for iniparib. No difference in sensitivity was observed between the TN and non-TN cell lines (by MTT). Olaparib also reduced the ability of cells to form colonies with IC50 values ranging from <0.01-2.5 µM. Addition of the CDKI inhibitor CDK1i (Calbiochem) to olaparib resulted in formation of significantly fewer colonies compared with either inhibitor alone, in a cell line dependent manner. Conclusions: Our results suggest that although PARP1 is expressed in the majority of breast cancer, significantly higher staining intensity was found in TN than non-TN samples. Furthermore, our work suggests that olaparib is a more potent inhibitor of the in vitro growth of breast cancer cells than iniparib. Combined inhibition of PARP1 with olaparib and CDK1 with CDK1i may be a way forward for the treatment of TNBC. Acknowledgement: The authors thank SFI (SRC award, 08/SRC/B1410 MTCI) for funding this work.

scholarly journals In Vitro Effects of Hemolymph Serum of Potamon persicum Crab (HSPPC) on MCF-7 and MDA-231 Breast Cancer Cell Lines

2019 ◽  
Vol 8 (2) ◽  
pp. 101-106
Author(s):  
Amin Mohammadi ◽  
Ali Mostafaie ◽  
Ahmad Bagheri ◽  
Sarah Kiani ◽  
Maryam Chalabi
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Dependent Manner ◽  
Cell Death Assay ◽  
Mcf 7

Background: Breast cancer is the most common cause of cancer-related death in women worldwide. Therefore, there is an urget need to identify and develop therapeutic strategies against this deadly disease. This study is the first to investigate the effects of Hemolymph Serum of Potamon persicum Crab (HSPPC) on MCF-7 and MDA-231 breast cancer cell lines. Materials and Methods: LDH and MTT assays were performed on MCF-7 and MDA-231 breast cancer cell lines as well as human umbilical vein endothelial cells (HUVEC) to determine the cytotoxic and antiproliferative activity of the HSPPC at different concentrations. Further, the apoptosis inducing action of the hemolymph serum was determined by TUNEL (terminal deoxynucleotidyl transferasemediated dUTP nick end labeling) and cell death assay. Results: The IC50 values of HSPPC for MCF-7 and MDA-231 cell lines were 960±0.369 and 850±1.422 μg/mL, respectively. The growth of both MCF-7 and MDA-231 cell lines were significantly (P<0.001) inhibited by HSPPC as compared with untreated controls at 48 hours. The results showed that HSPPC had no cytotoxic effects but significantly inhibited cell growth in a dose and time dependent manner. In addition, DNA fragmentation analysis (TUNEL) and cell death assay indicated induction of apoptosis by HSPPC in MCF-7 and MDA-231 cell lines. Conclusion: The results suggest that HSPPC contains bioactive compound(s) with potentials for the treatment of breast cancer.

scholarly journals The Arabian camel,Camelus dromedariusinterferon epsilon: functional expression,in vitrorefolding, purification and cytotoxicity on breast cancer cell lines MDA-MB-231 and MCF-7

2019 ◽  
Author(s):  
Manal Abdel-Fattah ◽  
Hesham Saeed ◽  
Lamiaa El-Shennawy ◽  
Manal Shalaby ◽  
Amira M. Embaby ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Inclusion Bodies ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Dependent Manner ◽  
Arabian Camel ◽  
Mcf 7

AbstractThe current study highlights for the first time cloning, overexpression, purification, and assessing the cytotxcity of the novel interferon epsilon (IFNε), from the Arabian camelCamelus dromedarius, against two human breast cancer cell lines MDA-MB-231 and MCF-7. Full-length cDNA encoding interferon epsilon (IFNε) was isolated and cloned from the liver of the Arabian camel,C. dromedariususing reverse transcription-polymerase chain reaction. The sequence analysis of the camel IFNε cDNA showed a 582-bp open reading frame encoding a protein of 193 amino acids with an estimated molecular weight of 22.953 kDa. A BLAST search analysis revealed that theC. dromedariusIFNε shared high sequence identity with the IFN genes of other species, such asCamelus ferus,Vicugna pacos, andHomo sapiens. Expression of the camel IFNε cDNA inEscherichia coligave a fusion protein band of 22.73 kDa after induction with either isopropyl β-D-1-thiogalactopyranoside or lactose for 5 h. Recombinant IFNε protein was overexpressed in the form of inclusion bodies that were easily solubilized and refolded using SDS and KCl. The solubilized inclusion bodies were purified to apparent homogeneity using nickel affinity chromatography. We examined the effect of IFNε on two breast cancer cell lines MDA-MB-231 and MCF-7. In both cell lines, IFNε inhibited cell survival in a dose dependent manner as observed by MTT assay, morphological changes and apoptosis assay. Caspase-3 expression level was found to be increased in MDA-MB-231 treated cells as compared to untreated cells.

scholarly journals Chalcones Repressed the AURKA and MDR Proteins Involved in Metastasis and Multiple Drug Resistance in Breast Cancer Cell Lines

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 2018 ◽  
Author(s):  
Tatiana Komoto ◽  
Tayná Bernardes ◽  
Thaís Mesquita ◽  
Luis Bortolotto ◽  
Gabriel Silva ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Dependent Manner ◽  
Licochalcone A ◽  
Mdr 1 ◽  
Mcf 7

In the present investigation, trans-chalcone and licochalcone A were tested against MCF-7 and BT-20 breast cancer cell lines for anti-tumor activity. We found that both chalcones down regulated important genes associated to cancer development and inhibited cell migration of metastatic cells (BT-20). Finally, we observed that licochalcone A reduces the MDR-1 protein, while both chalcones suppress the AURKA protein in a dose-dependent manner. In conclusion, we observed the trans-chalcone and licochalcone A affected the cell viability of breast cancer cell lines MCF-7 and BT-20 and presents anti-metastatic and anti-resistance potential, by the repression of AUKA and MDR-1 proteins.

The Enhanced Cytotoxic Effects of the p28-Apoptin Chimeric Protein As A Novel Anti-Cancer Agent on Breast Cancer Cell Lines

Drug Research ◽  
2018 ◽  
Vol 69 (03) ◽  
pp. 144-150 ◽  
Author(s):  
Ahmad Noei ◽  
Amir Nili-Ahmadabadi ◽  
Meysam Soleimani
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Chimeric Protein ◽  
Cancer Cell Lines ◽  
In Vivo Studies ◽  
Dimensional Structure ◽  
Breast Cancer Cell Lines ◽  
Dependent Manner

Abstract Backgrounds Peptide-based drugs have shown promising results in overcoming the limitations of chemotherapeutic drugs by providing a targeted therapy approach to cancer. However, the response rate of targeted therapies is limited, in large part due to the intra- and inter-heterogeneity of tumors. Methods In this study, we engineered a novel chimeric protein composed of the p28 peptide as a tumor-homing killer peptide and apoptin as a killer peptide. We evaluated its cytotoxicity against MCF7 and MDA-MB-231 breast cancer cells and HEK-293 normal cells by the MTT assay. Different linkers were evaluated when designing the chimeric protein. Three-dimensional structure predictions of chimeric proteins with different linkers were carried out by Modeller 9.19, and their validation and analysis were performed by RAMPAGE. Results Results showed that a cleavable linker, including furin cleavage sites, is preferred over other linkers. The chimeric protein was then successfully expressed in E. coli and purified by affinity chromatography under native conditions, then confirmed by SDS-PAGE and Western blot analysis. Compared with apoptin alone, the chimeric protein showed significantly higher toxicity against breast cancer cell lines in a dose-dependent manner. The IC50 values of the chimeric protein for MCF7 and MDA-MB-231 cells were 38.55 µg/mL and 43.11 µg/mL, respectively. There was no significant cytotoxic effect on the normal HEK293 cell line. Conclusion This study demonstrates that fusion of p28 peptide to a potent protein could provide an effective method for tumor targeting. Further, in vitro and in vivo studies of this novel chimeric protein are underway.

Cadmium telluride quantum dots induce apoptosis in human breast cancer cell lines

2018 ◽  
Vol 34 (5) ◽  
pp. 339-352 ◽  
Author(s):  
Saeed Naderi ◽  
Hakimeh Zare ◽  
Nima Taghavinia ◽  
Azam Irajizad ◽  
Mahmoud Aghaei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Annexin V ◽  
Cancer Cell Lines ◽  
High Yield ◽  
Breast Cancer Cell Lines ◽  
Dependent Manner ◽  
Cdte Qds

Introduction: Semiconductor quantum dots (QDs), especially those containing cadmium, have undergone marked improvements and are now widely used nanomaterials in applicable biological fields. However, great concerns exist regarding their toxicity in biomedical applications. Because of the lack of sufficient data regarding the toxicity mechanism of QDs, this study aimed to evaluate the cytotoxicity of three types of QDs: CdTe QDs, high yield CdTe QDs, and CdTe/CdS core/shell QDs on two human breast cancer cell lines MDA-MB468 and MCF-7. Methods: The breast cancer cells were treated with different concentrations of QDs, and cell viability was evaluated via MTT assay. Hoechst staining was applied for observation of morphological changes due to apoptosis. Apoptotic DNA fragmentation was visualized by the agarose gel electrophoresis assay. Flow cytometric annexin V/propidium iodide (PI) measurement was used for apoptosis detection. Results: A significant decrease in cell viability was observed after QDs treatment ( p < 0.05). Apoptotic bodies and chromatin condensation was observed by Hoechst staining. DNA fragmentation assay demonstrated a DNA ladder profile in the exposed cells and also annexin V/PI flow cytometry confirmed apoptosis in a dose-dependent manner. Conclusion: Our results revealed that CdTe, high yield CdTe, and CdTe/CdS core/shell QDs induce apoptosis in breast cancer cell lines in a dose-dependent manner. This study would help realizing the underlying cytotoxicity mechanism, at least partly, of CdTe QDs and may provide information for the development of nanotoxicology and safe use of biological applications of QDs.

scholarly journals The Tetramethylpyrazine Derivative Statmp-151: A Novel Small Molecule Stat3 Inhibitor With Promising Activity Against Breast Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Chen Fan ◽  
Yijie Wang ◽  
Hui Huang ◽  
Wenzhen Li ◽  
Jialin Ma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Potential Candidate ◽  
Dependent Manner ◽  
The Matrix

Breast cancer is the most common malignancy in women and is a molecularly heterogeneous disease. Signal transducer and activator of transcription 3 (Stat3) is overexpressed and hyperactivated in a variety of human tumours, including breast cancer, thus representing a promising target for breast cancer treatment. In the present study, we evaluated the activities of a novel Stat3 inhibitor named Statmp-151 in the human breast cancer cell lines MCF-7 and MDA-MB-231 and the murine mammary carcinoma cell line 4T1. The in vitro results showed that Statmp-151 inhibited the proliferation of breast cancer cell lines in a dose- and time-dependent manner and suppressed the phosphorylation of Stat3 in a dose-dependent manner. Flow cytometry (FCM) assays revealed that Statmp-151 affected mitochondrial membrane potential and reactive oxygen species (ROS) production. Furthermore, Statmp-151 inhibited cell migration, as shown by analysis of the matrix metalloproteinases MMP2 and MMP9. Finally, in a 4T1 tumour-bearing mouse model, intraperitoneal injection of 30 mg/kg/day Statmp-151 significantly suppressed the growth of tumours without obvious toxicity. These results indicated that Statmp-151 might be a potential candidate for the treatment of breast cancer.

Apoptotic Effect of Gemini Curcumin on MDA-MB-468 Breast Cancer Cell Line

2021 ◽  
Vol 21 ◽  
Author(s):  
Masoumeh Hajizadeh ◽  
Salar Hafez Ghoran ◽  
Hewa Jalal Azeez ◽  
Mohammad Ali Hosseinpour Feizi ◽  
Esmaeil Babaei
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Caspase 3 ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Dependent Manner ◽  
Expression Ratio ◽  
Apoptotic Effect

Background: Gemini Curcumin (Gemini-Cur) is the latest nano formulation of curcumin with a significant apoptotic effect on cancer cell lines. Objective: This in vitro study aims to evaluate the apoptotic effects of Gemini-Cur toward MDA-MB-468 breast cancer cell lines and further the related mechanism of apoptosis. Methods: The cytotoxicity of Gemini-Cur toward MDA-MB-468 cell lines was tested using MTT assay. Furthermore, the expression ratio of Bax/Bcl-2 was evaluated by qRT-PCR. Consequently, the protein expression of Bax/Bcl-2, survivin, and caspase-3 was measured using western blotting. Results: Having treated MDA-MB-468 cell lines with Gemini-Cur, the IC50 values were found to be 44.44 and 31.63 µM at 24 and 48 h, respectively. Our findings showed that Gemini-Cur significantly suppresses cancerous cell proliferation in a time- and dose-dependent manner. Furthermore, the data revealed that curcumin nanoformulation induces apoptosis in MDA-MB-468 cells through modulation of the expression of Bax, Bcl-2, Survivin, and Caspase-3. Conclusion: The data of the current study propose that Gemini-Cur can be considered a promising candidate against triple-negative breast cancer.

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