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 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 Methanol Extract of Usnea barbata Induces Cell Killing, Apoptosis, and DNA Damage against Oral Cancer Cells through Oxidative Stress

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 694
Author(s):  
Jen-Yang Tang ◽  
Kuang-Han Wu ◽  
Yen-Yun Wang ◽  
Ammad Ahmad Farooqi ◽  
Hurng-Wern Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Oral Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Time Course ◽  
Cell Killing ◽  
Parp Cleavage ◽  
Flow Cytometric ◽  
Oral Cancer Cells

Some lichens provide the resources of common traditional medicines and show anticancer effects. However, the anticancer effect of Usnproliea barbata (U. barbata) is rarely investigated, especially for oral cancer cells. The aim of this study was to investigate the cell killing function of methanol extracts of U. barbata (MEUB) against oral cancer cells. MEUB shows preferential killing against a number of oral cancer cell lines (Ca9-22, OECM-1, CAL 27, HSC3, and SCC9) but rarely affects normal oral cell lines (HGF-1). Ca9-22 and OECM-1 cells display the highest sensitivity to MEUB and were chosen for concentration effect and time course experiments to address its cytotoxic mechanisms. MEUB induces apoptosis of oral cancer cells in terms of the findings from flow cytometric assays and Western blotting, such as subG1 accumulation, annexin V detection, and pancaspase activation as well as poly (ADP-ribose) polymerase (PARP) cleavage. MEUB induces oxidative stress and DNA damage of oral cancer cells following flow cytometric assays, such as reactive oxygen species (ROS)/mitochondrial superoxide (MitoSOX) production, mitochondrial membrane potential (MMP) depletion as well as overexpression of γH2AX and 8-oxo-2′deoxyguanosine (8-oxodG). All MEUB-induced changes in oral cancer cells were triggered by oxidative stress which was validated by pretreatment with antioxidant N-acetylcysteine (NAC). In conclusion, MEUB causes preferential killing of oral cancer cells and is associated with oxidative stress, apoptosis, and DNA damage.

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

scholarly journals Naringenin inhibits human breast cancer cells (MDA-MB-231) by inducing programmed cell death, caspase stimulation, G2/M phase cell cycle arrest and suppresses cancer metastasis

2021 ◽  
Vol 67 (2) ◽  
pp. 8-13
Author(s):  
Zhaozhen Qi ◽  
Shuangxi Kong ◽  
Shunyu Zhao ◽  
Qiu Tang
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Apoptotic Cell ◽  
Flow Cytometric Analysis ◽  
Annexin V ◽  
Cycle Arrest ◽  
Flow Cytometric ◽  
M Phase

The current study was designed to unveil the anticancer effects of naringenin against breast cancer MDA-MB-231 cells. Cytotoxic effects were estimated via MTT viability assay. Clonogenic assay was performed to assess clonogenic potential of MDA-MB-231 cells. Apoptosis was examined via AO/EB staining, quantified via annexin V/PI staining and western blotting was performed to monitor apoptosis allied protein expressions. Cell cycle was analyzed through flow cytometric analysis. Transwell chambers assay was executed for determination of cell migration and cell invasion tendency of MDA-MB-231 breast cancer cells. Results indicated significant anticancer potential of naringenin drug against MDA-MB-231 cells. On evaluation of cell proliferation rate of breast cancer cells by MTT assay, it was observed that naringenin inhibited proliferation rate in dose as well as time dependent manner. AO/EB staining assay revealed potential morphological changes indicating apoptotic cell death. Annexin V/PI staining assay revealed increased apoptotic cell percentage with increased drug doses. The apoptosis inducing potential of naringenin drug was observed to be mediated via caspase activation. Flow cytometric analysis predicted cell cycle arrest at G2/M phase of cell cycle. Further cell migration as well as cell invasion tendency of MDA-MB-231 cells was reduced to minimum upon application of naringenin drug.

scholarly journals The Preliminary Study on the Proapoptotic Effect of Reduced Graphene Oxide in Breast Cancer Cell Lines

2021 ◽  
Vol 22 (22) ◽  
pp. 12593
Author(s):  
Rafał Krętowski ◽  
Agata Jabłońska-Trypuć ◽  
Marzanna Cechowska-Pasko
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Graphene Oxide ◽  
Cancer Cells ◽  
Reduced Graphene Oxide ◽  
Cell Lines ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines ◽  
Reduced Graphene

Breast cancer is the most common cancer diagnosed in women, however traditional therapies have several side effects. This has led to an urgent need to explore novel drug approaches to treatment strategies such as graphene-based nanomaterials such as reduced graphene oxide (rGO). It was noticed as a potential drug due to its target selectivity, easy functionalisation, chemisensitisation, and high drug-loading capacity. rGO is widely used in many fields, including biological and biomedical, due to its unique physicochemical properties. However, the possible mechanisms of rGO toxicity remain unclear. In this paper, we present findings on the cytotoxic and antiproliferative effects of rGO and its ability to induce oxidative stress and apoptosis of breast cancer cell lines. We indicate that rGO induced time- and dose-dependent cytotoxicity in MDA-MB-231 and ZR-75-1 cell lines, but not in T-47D, MCF-7, Hs 578T cell lines. In rGO-treated MDA-MB-231 and ZR-75-1 cell lines, we noticed increased induction of apoptosis and necrosis. In addition, rGO has been found to cause oxidative stress, reduce proliferation, and induce structural changes in breast cancer cells. Taken together, these studies provide new insight into the mechanism of oxidative stress and apoptosis in breast cancer cells.

scholarly journals Potassium channel inhibitors induce oxidative stress in breast cancer cells

2018 ◽  
Vol 11 (4) ◽  
pp. 323-330 ◽  
Author(s):  
Çağri Öner ◽  
Ertuğrul Çolak ◽  
Didem Turgut Coşan
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Potassium Channels ◽  
Potassium Channel ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Lines ◽  
Mcf 7

AbstractBackgroundAntioxidant levels increase to protect cell homeostasis when oxidant generation is increased by drug or inhibitor treatment. If the oxidant–antioxidant equilibrium is disrupted, oxidative stress will occur.ObjectivesTo determine the effects of various potassium channel inhibitors in the disruption of oxidant–antioxidant equilibrium in breast cancer cell lines with various phenotypes.MethodsMCF-7 or MDA-MB-231 breast cancer cells were treated with tetraethylammonium chloride (5 mM; TEA), 4-aminopyridine (5 mM; 4-AP), margatoxin (25 nM; MgTX), or astemizole (200 nM; AST). After treatment, total antioxidant, oxidant, and oxidative stress levels were determined.ResultsIncubation with TEA, 4-AP, MgTX, and AST increased oxidative stress in both MCF-7 and MDA-MB-231 cells (P < 0.001). Specific inhibitors of calcium-activated potassium channels and ether á go-go 1-related potassium channels produce greater oxidative stress than other inhibitors in MCF-7 breast cancer cells, whereas in MDA-MB-231 cells, the nonselective channel inhibitor 4-AP produces the greatest oxidative stress.ConclusionsPotassium channel inhibitors used in our study disrupted the antioxidant–oxidant equilibrium and increased oxidative stress in the cancer cell lines. Although all of the channel inhibitors increased oxidative stress in cells, TEA and AST were the most effective inhibitors in MCF-7 cells. 4-AP was the most effective inhibitor in MDA-MB-231 cells. Voltage-gated potassium channels are attractive targets for anticancer therapy, and their inhibitors may enhance the effects of anticancer drugs.

scholarly journals Autophagy-Mediated Clearance of Free Genomic DNA in the Cytoplasm Promoted the Growth and Survival of Breast Cancer Cells

2021 ◽  
Author(s):  
Mengfei Yao ◽  
Yaqian Wu ◽  
Yanan Cao ◽  
Haijing Liu ◽  
Ningning Ma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Cell Lines ◽  
Genomic Dna ◽  
Breast Cancer Cells ◽  
Statistical Tests ◽  
Breast Cancer Cell Lines ◽  
Growth And Survival ◽  
Selective Autophagy

Abstract Background: The cGAS (GMP-AMP synthase)-triggered senescence-associated secretory phenotype (SASP) in promotion of cancer progression has been extensively documented. However, the role of cGAS-mediated DNA autophagy is little evaluated in breast cancer cells.Methods: Immunofluorescence, senescence associated-β-galactosidase staining (SA-β-gal) and Western blot were performed to detect gene expression, distribution and phenotypes. PCR, IP-PCR, FISH, BrdU, Comet assay, coimmunoprecipitation, sucrose density gradient centrifugation were carried out to detect possible mechanisms. Trypan blue exclusion, Live/dead staining and MTS assay were to measure the cell viability. All analyses were performed using GraphPad Prism 8. Relationships were analyzed using t-tests. A P-value of less than 0.05 was considered significant. All statistical tests and P values were 2-sided, and the level of significance was set at <0.05 (*), <0.01 (**), <0.001 (***), or<0.0001 (****); ns indicates no significance.Results: Active DNA autophagy but not SASP activity could be detected in breast cancer cells with high micronucleus (MN). The selective autophagy of free genomic DNA in the cytoplasm is mediated by cGAS and usually coordinated with SQSTM1-mediated autophagy of ubiquitinated histones in breast cancer cell lines with high frequency of MN formation. Cytoplasmic DNA together with nuclear proteins derive from DNA replication-induced nuclear damage and MN collapse in breast cell lines which with severe DNA damage. The inhibition of DNA autophagy through either chemical inhibitors or genomic silencing of cGAS or SQSTM1 suppresses the growth and survival of breast cancer cells, while enhanced DNA damage increases the sensitivity to these inhibitors for more cancer cells. Human cancer cells with either high DNA autophagy or enhancement of DNA damage are sensitive to inhibition of DNA autophagy.Conclusions: Our investigation revealed DNA autophagy in breast cancer cells with high MN formation. Autophagy of genomic DNA in the cytosol could be mediated by cGAS but is usually coordinated with other autophagic mediators. The selective autophagy mediated clearance of free genomic DNA protects of growth and survival in breast cancer cells even, and autophagic inhibition could be a potential therapeutic approach for cancer cells with high DNA autophagic activity.

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 Circadian Rhythms and Breast Cancer: The Role of Per2 in Doxorubicin-Induced Cell Death

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Megan I. Mitchell ◽  
Anna-Mart Engelbrecht
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Circadian Rhythms ◽  
Cancer Cells ◽  
Cell Lines ◽  
Breast Cancer Cells ◽  
Normal Breast ◽  
Cytotoxic Effects ◽  
Downstream Effects

Mammalian circadian rhythms form an integral physiological system allowing for the synchronisation of all metabolic processes to daily light/dark cycles, thereby optimising their efficacy. Circadian disruptions have been implicated in the onset and progression of various cancers, including those arising in the breast. Several links between the circadian protein Per2 and DNA damage responses exist. Aberrant Per2 expression results in potent downstream effects on both cell cycle and apoptotic targets, suggestive of a tumour suppressive role for Per2. Due to the severe dose limiting side effects associated with current chemotherapeutic strategies, including the use of doxorubicin, a need for more effective adjuvant therapies to increase cancer cell susceptibility has arisen. This study was therefore aimed at characterizing the role of Per2 in normal breast epithelia (MCF-12A) and in ER−breast cancer cells (MDA-MB-231) and also at determining the role of Per2 in doxorubicin-induced cell death. In both cell lines Per2 protein expression displayed a 24-hour circadian rhythm in both cell lines. Per2 was located predominantly in the cytoplasm, with nuclear localization observed with lower cytoplasmic fluorescent intensities. Our results show that Per2 silencing effectively sensitizes the chemoresistant MDA-MB-231 breast cancer cells to the cytotoxic effects of doxorubicin.

Sign in / Sign up

Export Citation Format

Share Document