scholarly journals Physalis peruviana-Derived Physapruin A (PHA) Inhibits Breast Cancer Cell Proliferation and Induces Oxidative-Stress-Mediated Apoptosis and DNA Damage

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 393
Author(s):  
Tzu-Jung Yu ◽  
Yuan-Bin Cheng ◽  
Li-Ching Lin ◽  
Yi-Hong Tsai ◽  
Bo-Yi Yao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Flow Cytometry ◽  
Dna Damage ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Time Course ◽  
Growth Factor Receptor ◽  
Annexin V ◽  
Anticancer Properties

Breast cancer expresses clinically heterogeneous characteristics and requires multipurpose drug development for curing the different tumor subtypes. Many withanolides have been isolated from Physalis species showing anticancer effects, but the anticancer function of physapruin A (PHA) has rarely been investigated. In this study, the anticancer properties of PHA in breast cancer cells were examined by concentration and time-course experiments. In terms of cellular ATP content, PHA inhibited the proliferation of three kinds of breast cancer cells: MCF7 (estrogen receptor (ER)+, progesterone receptor (PR)+/−, human epidermal growth factor receptor 2 (HER2)−), SKBR3 (ER−/PR−/HER2+), and MDA-MB-231 (triple-negative). Moreover, PHA induced G2/M arrest in MCF7 and MDA-MB-231 cells. In terms of flow cytometry, PHA induced the generation of reactive oxygen species (ROS), the generation of mitochondrial superoxide, mitochondrial membrane potential depletion, and γH2AX-detected DNA damage in breast cancer MCF7 and MDA-MB-231 cells, which were suppressed by the ROS inhibitor N-acetylcysteine (NAC). In terms of flow cytometry and Western blotting, PHA induced apoptotic expression (annexin V, and intrinsic and extrinsic apoptotic signaling), which was suppressed by NAC and an apoptosis inhibitor (Z-VAD-FMK), in breast cancer cells. Therefore, PHA is a potential anti-breast-cancer natural product that modulates the oxidative-stress response, cell-cycle disturbance, apoptosis, and γH2AX-detected DNA damage.

scholarly journals Withanolide C Inhibits Proliferation of Breast Cancer Cells via Oxidative Stress-Mediated Apoptosis and DNA Damage

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 873
Author(s):  
Tzu-Jung Yu ◽  
Jen-Yang Tang ◽  
Li-Ching Lin ◽  
Wan-Ju Lien ◽  
Yuan-Bin Cheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Dna Damage ◽  
Cancer Cells ◽  
Cell Lines ◽  
Breast Cancer Cells ◽  
Annexin V ◽  
Normal Breast ◽  
Atp Depletion ◽  
Flow Cytometric

Some withanolides, particularly the family of steroidal lactones, show anticancer effects, but this is rarely reported for withanolide C (WHC)—especially anti-breast cancer effects. The subject of this study is to evaluate the ability of WHC to regulate the proliferation of breast cancer cells, using both time and concentration in treatment with WHC. In terms of ATP depletion, WHC induced more antiproliferation to three breast cancer cell lines, SKBR3, MCF7, and MDA-MB-231, than to normal breast M10 cell lines. SKBR3 and MCF7 cells showing higher sensitivity to WHC were used to explore the antiproliferation mechanism. Flow cytometric apoptosis analyses showed that subG1 phase and annexin V population were increased in breast cancer cells after WHC treatment. Western blotting showed that cleaved forms of the apoptotic proteins poly (ADP-ribose) polymerase (c-PARP) and cleaved caspase 3 (c-Cas 3) were increased in breast cancer cells. Flow cytometric oxidative stress analyses showed that WHC triggered reactive oxygen species (ROS) and mitochondrial superoxide (MitoSOX) production as well as glutathione depletion. In contrast, normal breast M10 cells showed lower levels of ROS and annexin V expression than breast cancer cells. Flow cytometric DNA damage analyses showed that WHC triggered γH2AX and 8-oxo-2′-deoxyguanosine (8-oxodG) expression in breast cancer cells. Moreover, N-acetylcysteine (NAC) pretreatment reverted oxidative stress-mediated ATP depletion, apoptosis, and DNA damage. Therefore, WHC kills breast cancer cells depending on oxidative stress-associated mechanisms.

scholarly journals Extracellular DNA Containing (dG)n Motifs Penetrates into MCF7 Breast Cancer Cells, Induces the Adaptive Response, and Can Be Expressed

2019 ◽  
Vol 2019 ◽  
pp. 1-16
Author(s):  
Ekaterina A. Kozhina ◽  
Elizaveta S. Ershova ◽  
Natalya A. Okorokova ◽  
Vladimir P. Veiko ◽  
Elena M. Malinovskaya ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Flow Cytometry ◽  
Dna Damage ◽  
Cancer Cells ◽  
Adaptive Response ◽  
Breast Cancer Cells ◽  
Fluorescent Microscopy ◽  
Ribosomal Genes ◽  
Extracellular Dna ◽  
Cmv Promoter

Background. Oxidized human DNA or plasmid DNAs containing human ribosomal genes can easily penetrate into the breast cancer cells MCF7 and stimulate the adaptive response induction. Plasmid DNA containing a CMV promoter, gene EGFP, and the insertion of the human ribosomal genes can be expressed. A hypothesis is proposed: these features of the ribosomal DNA are due to the presence of dGn motifs that are prone to oxidize. Methods. Cells of MCF7 line were cultured with plasmids which contained a CMV promoter and gene of fluorescent protein EGFP. Genetic construction pEGFP-Gn contains pEGFP vector and a small insertion with dG11 and dG13 motifs that are inclined to oxidation. The accumulation of pEGFP and pEGFP-Gn in MCF7 (qPCR), the levels of ROS in the cells, the content of 8-oxodG in plasmids and cellular DNA (flow cytometry, immunoassay, and fluorescent microscopy), the expression of NOX4 and EGFP, the localization of NOX4 and EGFP in MCF7 (qPCR, flow cytometry, and fluorescent microscopy), and the levels of the cell DNA damage (comet assay) were analyzed. Results. (dG)n insertions in the plasmid pEGFP increase the levels of ROS, the cell DNA oxidation and DNA damage, and the level of transfection of plasmid into the MCF7 cells. NOX4 participates in the oxidation of pEGFP-Gn and pEGFP. The expression of EGFP gene in MCF7 is significantly increased in case of pEGFP-Gn. Stimulation of ROS synthesis (H2O2 40 μM or 10 cGy IR) increases the level of expression of EGFP. Conclusions. GC-rich DNA fragments containing dGn motifs that are inclined to oxidation penetrate into MCF7 cancer cells, stimulate the adaptive response, and can be expressed. This property of GC-rich cell-free DNA should be considered and/or could potentially be used in therapy of tumors.

scholarly journals HuR silencing elicits oxidative stress and DNA damage and sensitizes human triple-negative breast cancer cells to radiotherapy

Oncotarget ◽  
2016 ◽  
Vol 7 (40) ◽  
pp. 64820-64835 ◽  
Author(s):  
Meghna Mehta ◽  
Kanthesh Basalingappa ◽  
James N. Griffith ◽  
Daniel Andrade ◽  
Anish Babu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Dna Damage ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative

Alkylamino Phenol Derivative Induces Apoptosis by Inhibiting EGFR Signaling Pathway in Breast Cancer Cells

2020 ◽  
Vol 20 (7) ◽  
pp. 809-819 ◽  
Author(s):  
Suresh Palanivel ◽  
Olli Yli-Harja ◽  
Meenakshisundaram Kandhavelu
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Breast Cancer Cells ◽  
Growth Factor Receptor ◽  
Annexin V ◽  
Binding Mode ◽  
Quantitative Structure Activity Relationship ◽  
Phenol Derivative ◽  
Egfr Signaling Pathway

Background and Objective: The present study was carried out to evaluate the anticancer property of an alkylamino phenol derivative -2-((3,4-Dihydroquinolin-1(2H)-yl)(p-tolyl)methyl)phenol) (THTMP) against human breast cancer cells. The cytotoxicity of the THTMP was assessed to know its specificity towards breast cancer cells without affecting the normal cells. Methods: The THTMP was synthesized and the cytotoxicity was assessed by MTT assay, Caspases enzyme activity, DNA fragmentation and FITC/Annexin V, AO/EtBr staining, RT-PCR and QSAR. In addition, ADME analysis was executed to understand the mode of action of THTMP. Results: THTMP showed potential cytotoxic activity against the growth of MCF7 and SK-BR3 cells with the IC50 values of 87.92μM and 172.51μM, respectively. Interestingly, THTMP found to activate caspase 3 and caspase 9 enzymes in cancer cells, which are the key enzymes implicated in apoptosis. THTMP induced apoptosis in which 33% of the cells entered the late apoptotic stage after 24h of treatment. The results also revealed that the apoptotic response could be influenced by the association of THTMP with the Epidermal Growth Factor Receptor (EGFR) mediated inhibition of the Phosphatidylinositol 3-Kinase (PI3K)/S6K1 signaling pathway. In addition, docking was performed to study the binding mode of the THTMP, which shows better interaction with EGFR. The structural elucidation of THTMP by Quantitative Structure-Activity Relationship model (QSAR) and ADMET screening suggested, THTMP as an effective anticancer compound. Conclusion: This work strengthens the potential of a promising drug-like compound, THTMP, for the discovery of anticancer drug against breast cancer.

scholarly journals Antiproliferation for Breast Cancer Cells by Ethyl Acetate Extract of Nepenthes thorellii x (ventricosa x maxima)

2019 ◽  
Vol 20 (13) ◽  
pp. 3238 ◽  
Author(s):  
Fu Ou-Yang ◽  
I-Hsuan Tsai ◽  
Jen-Yang Tang ◽  
Ching-Yu Yen ◽  
Yuan-Bin Cheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Dna Damage ◽  
Ethyl Acetate ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Ethyl Acetate Extract ◽  
Mechanistic Study ◽  
Breast Cancer Cell Lines ◽  
Antitumor Effects

Extracts from the Nepenthes plant have anti-microorganism and anti-inflammation effects. However, the anticancer effect of the Nepenthes plant is rarely reported, especially for breast cancer cells. Here, we evaluate the antitumor effects of the ethyl acetate extract of Nepenthes thorellii x (ventricosa x maxima) (EANT) against breast cancer cells. Cell viability and flow cytometric analyses were used to analyze apoptosis, oxidative stress, and DNA damage. EANT exhibits a higher antiproliferation ability to two breast cancer cell lines (MCF7 and SKBR3) as compared to normal breast cells (M10). A mechanistic study demonstrates that EANT induces apoptosis in breast cancer cells with evidence of subG1 accumulation and annexin V increment. EANT also induces glutathione (GSH) depletion, resulting in dramatic accumulations of reactive oxygen species (ROS) and mitochondrial superoxide (MitoSOX), as well as the depletion of mitochondrial membrane potential (MMP). These oxidative stresses attack DNA, respectively leading to DNA double strand breaks and oxidative DNA damage in γH2AX and 8-oxo-2′deoxyguanosine (8-oxodG) assays. Overall these findings clearly revealed that EANT induced changes were suppressed by the ROS inhibitor. In conclusion, our results have shown that the ROS-modulating natural product (EANT) has antiproliferation activity against breast cancer cells through apoptosis, oxidative stress, and DNA damage.

scholarly journals Cytotoxic and apoptosis inducing effect of some pyrano [3, 2-c] pyridine derivatives against MCF-7 Breast Cancer Cells

2018 ◽  
Vol 65 (3) ◽  
Author(s):  
Mohammad Rahnamay ◽  
Majid Mahdavi ◽  
Ali Akbar Shekarchi ◽  
Payman Zare ◽  
Mohammad Ali Hosseinpour Feizi
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Time Course ◽  
Annexin V ◽  
Cell Cycle Analysis ◽  
Outer Cell ◽  
Dependent Manner ◽  
Mcf 7

Anti-cancer activities of some pyrano-pyridines have been previously reported. Herein, we investigated anti-proliferative and apoptotic effects of the novel pyrano [3, 2-c] pyridine (P.P, TPM.P, 4-CP.P and 3-NP.P) compounds against MCF-7 breast cancer cells. The MCF-7 cells were cultured in the presence of various concentrations (20-200 μM) of the compounds for 3 days and the cell viability was determined by MTT assay. Induction of apoptosis was qualitatively assayed by acridine orange/ethidium bromide (AO/EtBr) staining, DNA fragmentation assay, as well as quantitatively by Annexin V/PI double staining and cell cycle analysis. These compounds inhibited growth and proliferation of the MCF-7 cells in a dose- and time-dependent manner. The IC50 values of P.P, TPM.P, 4-CP.P and 3-NP.P after 24 h of exposure were calculated 100 ±5.0, 180 ±6.0, 60 ±4.0 and 140 ±5.0 μM, respectively. 4-CP.P was determined as stronger compound and was chosen for further studies. The result of flow cytometric cell cycle analysis indicated an increase in sub-G1 population after 72 h treatment of the cells. Furthermore, it was accompanied with exposure of phosphatidylserine (PS) in the outer cell membrane after time course of treatment with the 4-CP.P. Based on these observations, the pyrano [3, 2-c] pyridines can be regarded as a valuable candidate for further pharmaceutical evaluations.Anti-cancer activities of some pyrano-pyridines have been previously reported. Herein, we investigated anti-proliferative and apoptotic effects of the novel pyrano [3, 2-c] pyridine (P.P, TPM.P, 4-CP.P and 3-NP.P) compounds against MCF-7 breast cancer cells. The MCF-7 cells were cultured in the presence of various concentrations (20-200 μM) of the compounds for 3 days and the cell viability was determined by MTT assay. Induction of apoptosis was qualitatively assayed by acridine orange/ethidium bromide (AO/EtBr) staining, DNA fragmentation assay, as well as quantitatively by Annexin V/PI double staining and cell cycle analysis. These compounds inhibited growth and proliferation of the MCF-7 cells in a dose- and time-dependent manner. The IC50 values of P.P, TPM.P, 4-CP.P and 3-NP.P after 24 h of exposure were calculated 100 ±5.0, 180 ±6.0, 60 ±4.0 and 140 ±5.0 μM, respectively. 4-CP.P was determined as stronger compound and was chosen for further studies. The result of flow cytometric cell cycle analysis indicated an increase in sub-G1 population after 72 h treatment of the cells. Furthermore, it was accompanied with exposure of phosphatidylserine (PS) in the outer cell membrane after time course of treatment with the 4-CP.P. Based on these observations, the pyrano [3, 2-c] pyridines can be regarded as a valuable candidate for further pharmaceutical evaluations.

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