scholarly journals In VitroUltrastructural Changes of MCF-7 for Metastasise Bone Cancer and Induction of Apoptosis via Mitochondrial Cytochrome C Released by CaCO3/Dox Nanocrystals

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Abdullahi Shafiu Kamba ◽  
Maznah Ismail ◽  
Tengku Azmi Tengku Ibrahim ◽  
Zuki Abu Bakar Zakaria ◽  
Lawal Hassan Gusau
Keyword(s):  
Breast Cancer ◽  
Cytochrome C ◽  
Dna Fragmentation ◽  
Morphological Changes ◽  
Chromatin Condensation ◽  
Bone Cancer ◽  
Breast Cancers ◽  
Chromosomal Dna ◽  
Substantial Impact ◽  
Mcf 7

Bones are the most frequent site for breast cancer cells to settle and spread (metastasise); bone metastasis is considered to have a substantial impact on the quality of patients with common cancers. However, majority of breast cancers develop insensitivity to conventional chemotherapy which provides only palliation and can induce systemic side effects. In this study we evaluated the effect of free Dox and CaCO3/Dox nanocrystal on MCF-7 breast cancer using MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide), neural red, and lactate dehydrogenase colorimetric assays while DNA fragmentation and BrdU genotoxicity were also examined. Apoptogenic protein Bax, cytochrome C, and caspase-3 protein were analysed. Morphological changes of MCF-7 were determined using contrast light microscope and scanning and transmission electron microscope (SEM and TEM). The findings of the analysis revealed higher toxicity of CaCO3/Dox nanocrystal and effective cells killing compared to free Dox, morphological changes such as formation of apoptotic bodies, membrane blebbing, and absent of microvilli as indicated by the SEM analysis while TEM revealed the presence of chromatin condensation, chromosomal DNA fragmentation, cell shrinkage, and nuclear fragmentation. Results of TUNEL assay verified that most of the cells undergoes apoptosis by internucleosomal fragmentation of genomic DNA whereas the extent of apoptotic cells was calculated using the apoptotic index (AI). Therefore, the biobased calcium carbonate nanocrystals such as Dox carriers may serve as an alternative to conventional delivery system.

scholarly journals The Role of Aryl Hydrocarbon Receptor and Crosstalk with Estrogen Receptor in Response of Breast Cancer Cells to the Novel Antitumor Agents Benzothiazoles and Aminoflavone

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Mariana A. Callero ◽  
Andrea I. Loaiza-Pérez
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Aryl Hydrocarbon Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Antitumor Agents ◽  
Breast Cancers ◽  
Nude Mouse Model ◽  
Aryl Hydrocarbon ◽  
Mcf 7

Many estrogen-receptor- (ER-) expressing breast cancers become refractory to ER-based therapies. New antitumor drugs like aminoflavone (AF) and benzothiazoles (Bzs) have been developed and have exquisite antitumor activity in ER+MCF-7 and T47D cells and in a MCF-7 nude mouse model. ER(−) breast cancer cells like MDA-MB-231 are less susceptible. We previously found in MCF-7 cells that these drugs activate the aryl hydrocarbon receptor (AhR) via translocation to the nucleus, induction of AhR-specific DNA binding activity, and expression of CYP1A1, whose transcription is controlled by the AhR-ARNT transcription factor. CYP1A1 metabolizes AF and Bz to a species which directly or after further metabolism damages DNA. In contrast an AhR-deficient variant of MCF-7 or cells with predominantly nuclear AhR expression, such as MDA-MB 231, are resistant. Thus, these drugs, unlike other neoplastic agents, require AhR-mediated signaling to cause DNA damage. This is a new treatment strategy for breast cancers with intact AhR signaling.

scholarly journals Carbidopa Alters Tryptophan Metabolism in Breast Cancer and Melanoma Cells Leading to the Formation of Indole-3-Acetonitrile, a Pro-Proliferative Metabolite

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 409
Author(s):  
Diana Duarte ◽  
Filipa Amaro ◽  
Isabel Silva ◽  
Dany Silva ◽  
Paula Fresco ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Cell Lines ◽  
Lower Incidence ◽  
Metabolic Profile ◽  
Dopa Decarboxylase ◽  
Breast Cancers ◽  
Mcf 7 ◽  
A375 Cells

Carbidopa is used for the treatment of Parkinson’s disease (PD) as an inhibitor of DOPA decarboxylase, and PD patients taking carbidopa have a lower incidence of various tumors, except for breast cancer and melanoma. Recently, it was shown that carbidopa inhibits tryptophan-2,3-dioxygenase (TDO) and kynureninase enzymes. In the present study, the effect of carbidopa on the viability and metabolic profile of breast cancer MCF-7 and melanoma A375 cells was investigated. Carbidopa was not effective in inhibiting MCF-7 and A375 proliferation. Liquid chromatography and mass spectrometry revealed a new compound, identified as indole-3-acetonitrile (IAN), which promoted a concentration-dependent increase in the viability of both cell lines. The results suggest that treatment with carbidopa may alter tryptophan (Trp) metabolism in breast cancer and melanoma leading to the formation of a pro-proliferative Trp metabolite, which may contribute to its failure in reducing breast cancers and melanoma incidence in PD patients taking carbidopa.

Effects of the Gold Nanoparticles (AuNPs) on the Proliferation and Morphological Characteristics of Human Breast Cancer Cells (MCF-7) in Culture

2017 ◽  
Vol 268 ◽  
pp. 254-258 ◽  
Author(s):  
Nur Shafawati Rosli ◽  
Azhar Abdul Rahman ◽  
Azlan Abdul Aziz ◽  
Shaharum Shamsuddin ◽  
Nurul Sabihah Zakaria
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Culture Media ◽  
Morphological Changes ◽  
Morphological Characteristics ◽  
Morphological Observation ◽  
Duration Of Treatment ◽  
Significant Difference ◽  
Mcf 7

Ultrastructural characteristic and morphological changes of untreated and treated breast cancer MCF-7 cells were observed by energy-filtered transmission electron microscope (EFTEM). Morphological observation of MCF-7 after being treated with 13 nm, 50 nm, and 70 nm AuNPs, were looking unhealthy and dying out of the populace, the observed cells were more reduced and dying as treatment with 50 nm and 70 nm AuNPs. Cells detachment, clumping, shrunken, and dispersed cells in the culture medium and floating cells were also observed. The observed morphological changes increase in 50 nm and 70 nm AuNPs than in 13 nm AuNPs, which is less toxic to MCF-7 cells. The presented morphological analysis has established that 13 nm AuNPs showed less toxic to MCF-7 breast cancer cells. Whereas, control cells of MCF-7 were treated with only complete culture media, despite the duration of treatment, whereby the cells maintained most of their morphological features and observed to have a typical morphology of healthy cells that are well attached to the surface. These results indicate that AuNPs were clustered in the cells and there was no significant difference between images of different sizes of AuNPs observed in the cells, because the AuNPs always clustered together inside the cells.

scholarly journals Evaluation of Antiproliferative Activity of Red Sorghum Bran Anthocyanin on a Human Breast Cancer Cell Line (MCF-7)

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
P. Suganya Devi ◽  
M. Saravana Kumar ◽  
S. Mohan Das
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Human Breast Cancer ◽  
Morphological Changes ◽  
Cancer Cell Line ◽  
Human Breast Cancer Cell ◽  
Human Breast ◽  
Sorghum Bran ◽  
Mcf 7

Breast cancer is a leading cause of death in women worldwide both in the developed and developing countries. Thus effective treatment of breast cancer with potential antitumour drugs is important. In this paper, human breast cancer cell line MCF-7 has been employed to evaluate the antiproliferative activity of red sorghum bran anthocyanin. The present investigation showed that red sorghum bran anthocyanin induced growth inhibition of MCF-7 cells at significant level. The growth inhibition is dose dependent and irreversible in nature. When MCF-7 cells were treated with red sorghum bran anthocyanins due to activity of anthocyanin morphological changes were observed. The morphological changes were identified through the formation of apoptopic bodies. The fragmentation by these anthocyanins on DNA to oligonuleosomal-sized fragments, is a characteristic of apoptosis, and it was observed as concentration-dependent. Thus, this paper clearly demonstrates that human breast cancer cell MCF-7 is highly responsive by red sorghum bran anthocyanins result from the induction of apoptosis in MCF-7 cells.

scholarly journals Cytotoxicity and Proapoptotic Effects of Allium atroviolaceum Flower Extract by Modulating Cell Cycle Arrest and Caspase-Dependent and p53-Independent Pathway in Breast Cancer Cell Lines

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Somayeh Khazaei ◽  
Roslida Abdul Hamid ◽  
Vasudevan Ramachandran ◽  
Norhaizan Mohd Esa ◽  
Ashok Kumar Pandurangan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Morphological Changes ◽  
Fluorescent Microscopy ◽  
Breast Cancer Cell Lines ◽  
Herbaceous Plant ◽  
Dependent Manner ◽  
Flower Extract ◽  
Phase Arrest ◽  
Mcf 7

Breast cancer is the second leading cause of cancer death among women and despite significant advances in therapy, it remains a critical health problem worldwide. Allium atroviolaceum is an herbaceous plant, with limited information about the therapeutic capability. We aimed to study the anticancer effect of flower extract and the mechanisms of action in MCF-7 and MDA-MB-231. The extract inhibits the proliferation of the cells in a time- and dose-dependent manner. The underlying mechanism involved the stimulation of S and G2/M phase arrest in MCF-7 and S phase arrest in MDA-MB-231 associated with decreased level of Cdk1, in a p53-independent pathway. Furthermore, the extract induces apoptosis in both cell lines, as indicated by the percentage of sub-G0 population, the morphological changes observed by phase contrast and fluorescent microscopy, and increase in Annexin-V-positive cells. The apoptosis induction was related to downregulation of Bcl-2 and also likely to be caspase-dependent. Moreover, the combination of the extract and tamoxifen exhibits synergistic effect, suggesting that it can complement current chemotherapy. LC-MS analysis displayed 17 major compounds in the extract which might be responsible for the observed effects. Overall, this study demonstrates the potential applications of Allium atroviolaceum extract as an anticancer drug for breast cancer treatment.

scholarly journals TRAIL-Induced Apoptosis in TRAIL-Resistant Breast Carcinoma Through Quercetin Cotreatment

2018 ◽  
Vol 12 ◽  
pp. 117822341774985 ◽  
Author(s):  
Jasmine M Manouchehri ◽  
Katherine A Turner ◽  
Michael Kalafatis
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Human Tumor ◽  
Breast Cancers ◽  
Treatment Regimens ◽  
Efficacious Treatment ◽  
Induced Apoptosis ◽  
Necrosis Factor ◽  
Mcf 7

Breast cancer is the most commonly diagnosed cancer in women. There is a continued interest for the development of more efficacious treatment regimens for breast carcinoma. Recombinant human tumor necrosis factor–related apoptosis-inducing ligand (rhTRAIL) shows potential as a potent anticancer therapeutic for the treatment of breast cancer, whereas displaying minimal toxicity to normal cells. However, the promise of rhTRAIL for the treatment of breast cancer is dismissed by the resistance to rhTRAIL-induced apoptosis exhibited by many breast cancers. Thus, a cotreatment strategy was examined by applying the natural compound quercetin (Q) as a sensitizing agent for rhTRAIL-resistant breast cancer BT-20 and MCF-7 cells. Quercetin was able to sensitize rhTRAIL-resistant breast cancers to rhTRAIL-induced apoptosis as detected by Western blotting through the proteasome-mediated degradation of c-FLIPL and through the upregulation of DR5 expression transcriptionally. Overall, these in vitro findings establish that Q is an effective sensitizing agent for rhTRAIL-resistant breast cancers.

scholarly journals Fas Induces Cytoplasmic Apoptotic Responses and Activation of the MKK7-JNK/SAPK and MKK6-p38 Pathways Independent of CPP32-like Proteases

1997 ◽  
Vol 139 (4) ◽  
pp. 1005-1015 ◽  
Author(s):  
Fumiko Toyoshima ◽  
Tetsuo Moriguchi ◽  
Eisuke Nishida
Keyword(s):  
Cell Death ◽  
Dna Fragmentation ◽  
Morphological Changes ◽  
Chromatin Condensation ◽  
Cysteine Proteases ◽  
Cellular Responses ◽  
Jurkat Cells ◽  
Mitogen Activated Protein Kinase ◽  
Fas Signaling ◽  
Induced Apoptosis

IL-1β converting enzyme (ICE) family cysteine proteases are subdivided into three groups; ICE-, CPP32-, and Ich-1–like proteases. In Fas-induced apoptosis, activation of ICE-like proteases is followed by activation of CPP32-like proteases which is thought to be essential for execution of the cell death. It was recently reported that two subfamily members of the mitogen-activated protein kinase superfamily, JNK/SAPK and p38, are activated during Fas-induced apoptosis. Here, we have shown that MKK7, but not SEK1/ MKK4, is activated by Fas as an activator for JNK/ SAPK and that MKK6 is a major activator for p38 in Fas signaling. Then, to dissect various cellular responses induced by Fas, we used several peptide inhibitors for ICE family proteases in Fas-treated Jurkat cells and KB cells. While Z-VAD-FK which inhibited almost all the Fas-induced cellular responses blocked the activation of JNK/SAPK and p38, Ac-DEVD-CHO and Z-DEVD-FK, specific inhibitors for CPP32-like proteases, which inhibited the Fas-induced chromatin condensation and DNA fragmentation did not block the activation of JNK/SAPK and p38. Interestingly, these DEVD-type inhibitors did not block the Fas-induced morphological changes (cell shrinkage and surface blebbing), induction of Apo2.7 antigen, or the cell death (as assessed by the dye exclusion ability). These results suggest that the Fas-induced activation of the JNK/SAPK and p38 signaling pathways does not require CPP32-like proteases and that CPP32-like proteases, although essential for apoptotic nuclear events (such as chromatin condensation and DNA fragmentation), are not required for other apoptotic events in the cytoplasm or the cell death itself. Thus, the Fas signaling pathway diverges into multiple, separate processes, each of which may be responsible for part of the apoptotic cellular responses.

Estrogen-Regulated Genes Predict Survival in Hormone Receptor–Positive Breast Cancers

2006 ◽  
Vol 24 (11) ◽  
pp. 1656-1664 ◽  
Author(s):  
Daniel S. Oh ◽  
Melissa A. Troester ◽  
Jerry Usary ◽  
Zhiyuan Hu ◽  
Xiaping He ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Published Data ◽  
Data Sets ◽  
Breast Cancers ◽  
Outcome Predictor ◽  
Training Set ◽  
Hormone Receptor Positive ◽  
Prognosis Group ◽  
Mcf 7

Purpose The prognosis of a patient with estrogen receptor (ER) and/or progesterone receptor (PR) –positive breast cancer can be highly variable. Therefore, we developed a gene expression–based outcome predictor for ER+ and/or PR+ (ie, luminal) breast cancer patients using biologic differences among these tumors. Materials and Methods The ER+ MCF-7 breast cancer cell line was treated with 17β-estradiol to identify estrogen-regulated genes. These genes were used to develop an outcome predictor on a training set of 65 luminal epithelial primary breast carcinomas. The outcome predictor was then validated on three independent published data sets. Results The estrogen-induced gene set identified in MCF-7 cells was used to hierarchically cluster a 65 tumor training set into two groups, which showed significant differences in survival (P = .0004). Supervised analyses identified 822 genes that optimally defined these two groups, with the poor-prognosis group IIE showing high expression of cell proliferation and antiapoptosis genes. The good prognosis group IE showed high expression of estrogen- and GATA3-regulated genes. Mean expression profiles (ie, centroids) created for each group were applied to ER+ and/or PR+ tumors from three published data sets. For all data sets, Kaplan-Meier survival analyses showed significant differences in relapse-free and overall survival between group IE and IIE tumors. Multivariate Cox analysis of the largest test data set showed that this predictor added significant prognostic information independent of standard clinical predictors and other gene expression–based predictors. Conclusion This study provides new biologic information concerning differences within hormone receptor–positive breast cancers and a means of predicting long-term outcomes in tamoxifen-treated patients.

scholarly journals Anti cancer activity of Trachyspermum ammi against MCF7 cell lines mediates by p53 and Bcl-2 mRNA levels

2017 ◽  
Vol 6 (2) ◽  
pp. 78-83
Author(s):  
N Ramya ◽  
◽  
Priyadharshini ◽  
R Prakash ◽  
R Dhivya ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Dna Fragmentation ◽  
Cell Lines ◽  
Ethanolic Extract ◽  
Mrna Levels ◽  
Trachyspermum Ammi ◽  
Anti Cancer ◽  
Cancer Activity ◽  
Mcf 7

Breast cancer is second most common in women and accounts for 23% of all occurring cancers in women. Patients with breast cancer have increasingly shown resistance and high toxicity to chemotherapeutic drugs. Plant-derived products have proved to be an important source of anti-cancer drugs. The present study was to investigate the anti cancer activity of ethanolic extract of Trachyspermum ammi against MCF-7 cell lines. The preliminary phytochemical studies of ethanolic extract of Trachyspermum ammi showed the presence of flavanoids, alkaloids, glycosides, steroids, carbohydrates, phenols, tannins and terpenes. The IC50 concentration of ethanolic extract of Trachyspermum ammi was determined by MTT assay. The results showed the greater degree of cytotoxicity at the dose of 25µg/ml of Trachyspermum ammi and it has been taken as IC50 value for our further study. Then, we also evaluated the apoptotic effect by measuring the morphological changes, cell viability rates using light and fluorescent microscopical studies and DNA fragmentation by using gel electrophoresis method. The ethanolic extract of Trachyspermum ammi showed significant signs of apoptosis such as cell shrinkage, membrane blebbing and nuclei DNA fragmentation. Further, we analyze the gene expression mRNA levels by using RT-PCR method, it showed the expression of p53 was significantly (P<0.001) increased when compared with normal MCF-7 cell line. The expression of anti apoptotic gene Bcl-2 was significantly (P<0.01) reduced when compared with MCF-7 cell line. From this study we conclude that ethanolic extract of Trachyspermum ammi having significant anticancer activity against MCF-7 cell lines and it might be good therapeutic value for further investigation to develop natural compounds as a anti tumor agents.

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