scholarly journals Arsenic hexoxide has differential effects on cell proliferation and genome-wide gene expression in human primary mammary epithelial and MCF7 cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Donguk Kim ◽  
Na Yeon Park ◽  
Keunsoo Kang ◽  
Stuart K. Calderwood ◽  
Dong-Hyung Cho ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Mammary Epithelial ◽  
Mcf7 Cells ◽  
Differential Effects ◽  
Cycle Arrest ◽  
Genome Wide ◽  
Human Mammary Epithelial ◽  
Genome Wide Gene Expression

AbstractArsenic is reportedly a biphasic inorganic compound for its toxicity and anticancer effects in humans. Recent studies have shown that certain arsenic compounds including arsenic hexoxide (AS4O6; hereafter, AS6) induce programmed cell death and cell cycle arrest in human cancer cells and murine cancer models. However, the mechanisms by which AS6 suppresses cancer cells are incompletely understood. In this study, we report the mechanisms of AS6 through transcriptome analyses. In particular, the cytotoxicity and global gene expression regulation by AS6 were compared in human normal and cancer breast epithelial cells. Using RNA-sequencing and bioinformatics analyses, differentially expressed genes in significantly affected biological pathways in these cell types were validated by real-time quantitative polymerase chain reaction and immunoblotting assays. Our data show markedly differential effects of AS6 on cytotoxicity and gene expression in human mammary epithelial normal cells (HUMEC) and Michigan Cancer Foundation 7 (MCF7), a human mammary epithelial cancer cell line. AS6 selectively arrests cell growth and induces cell death in MCF7 cells without affecting the growth of HUMEC in a dose-dependent manner. AS6 alters the transcription of a large number of genes in MCF7 cells, but much fewer genes in HUMEC. Importantly, we found that the cell proliferation, cell cycle, and DNA repair pathways are significantly suppressed whereas cellular stress response and apoptotic pathways increase in AS6-treated MCF7 cells. Together, we provide the first evidence of differential effects of AS6 on normal and cancerous breast epithelial cells, suggesting that AS6 at moderate concentrations induces cell cycle arrest and apoptosis through modulating genome-wide gene expression, leading to compromised DNA repair and increased genome instability selectively in human breast cancer cells.

scholarly journals Arsenic hexoxide has differential effects on cell proliferation and genome-wide gene expression in human primary mammary epithelial and MCF7 cells

2021 ◽  
Author(s):  
Donguk Kim ◽  
Na Yeon Park ◽  
Keunsoo Kang ◽  
Stuart K. Calderwood ◽  
Dong-Hyung Cho ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Mammary Epithelial ◽  
Mcf7 Cells ◽  
Differential Effects ◽  
Cycle Arrest ◽  
Genome Wide ◽  
Human Mammary Epithelial ◽  
Genome Wide Gene Expression

ABSTRACTArsenic is reportedly a biphasic inorganic compound for its toxicity and anticancer effects in humans [1, 2]. Recent studies have shown that certain arsenic compounds including arsenic hexoxide (AS4O6; hereafter, AS6) induce programmed cell death and cell cycle arrest in human cancer cells and murine cancer models [3, 4]. However, the mechanisms by which AS6 suppresses cancer cells are incompletely understood. In this study, we report the mechanisms of AS6 through transcriptome analyses. In particular, the cytotoxicity and global gene expression regulation by AS6 were compared in human normal and cancer breast epithelial cells. Using RNA-sequencing and bioinformatics analyses, differentially expressed genes in significantly affected biological pathways in these cell types were validated by real-time quantitative polymerase chain reaction and immunoblotting assays. Our data show markedly differential effects of AS6 on cytotoxicity and gene expression in human mammary epithelial normal cells (HUMEC) and Michigan Cancer Foundation 7 (MCF7), a human mammary epithelial cancer cell line. AS6 selectively arrests cell growth and induces cell death in MCF7 cells without affecting the growth of HUMEC in a dose-dependent manner. AS6 alters the transcription of a large number of genes in MCF7 cells, but much fewer genes in HUMEC. Importantly, we found that the cell proliferation, cell cycle, and DNA repair pathways are significantly suppressed whereas cellular stress response and apoptotic pathways increase in AS6-treated MCF7 cells. Together, we provide the first evidence of differential effects of AS6 on normal and cancerous breast epithelial cells, suggesting that AS6 at moderate concentrations induces cell cycle arrest and apoptosis through modulating genome-wide gene expression, leading to compromised DNA repair and increased genome instability selectively in human breast cancer cells.

scholarly journals Senescent Colon and Breast Cancer Cells Induced by Doxorubicin Exhibit Enhanced Sensitivity to Curcumin, Caffeine, and Thymoquinone

2020 ◽  
Vol 19 ◽  
pp. 153473541990116 ◽  
Author(s):  
Ali H. El-Far ◽  
Noureldien H. E. Darwish ◽  
Shaker A. Mousa
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Cellular Senescence ◽  
Annexin V ◽  
Mcf7 Cells ◽  
Enhanced Sensitivity ◽  
Cycle Arrest

Cellular senescence is a process of physiological growth arrest that can be induced by intrinsic or extrinsic stress signals. Some cancer therapies are associated with senescence of cancer cells with a typical cell cycle arrest. Doxorubicin (Dox) induces senescence by a p53-dependent pathway and telomere dysfunction of numerous cancers. However, cellular senescence induces suppression in proliferation activity, and these cells will remain metabolically active and play an important role in tumor relapse and development of drug resistance. In the current study, we investigated the apoptotic effect of curcumin (Cur), caffeine (Caff), and thymoquinone (TQ) on senescent colon cancer HCT116 and breast cancer MCF7 cell lines treated with Dox. Results showed typical senescence markers including decreased bromodeoxyuridine incorporation, increased accumulation of senescence-associated β-galactosidase (SA-β-gal), cell cycle arrest, and upregulation of p53, P-p53, and p21 proteins. Annexin-V analysis by flow cytometry revealed 2- to 6-fold increases in annexin-V–positive cells in Dox-treated MCF7 and HCT116 cells by Cur (15 µM), Caff (10 mM), and TQ (50 µM; P < .001). In comparison between proliferative and senescent of either HCT116 or MCF7 cells, Caff at 15 mM and TQ at 25 µM induced significant increases in apoptosis of Dox-treated cells compared with proliferative cells ( P < .001). Data revealed that Cur, Caff, and TQ potentially induced apoptosis of both proliferative and senescent HCT116 and MCF7 cells. In vivo and clinical trials are of great importance to validate this result.

The C. elegans homolog of the Evi1 proto-oncogene, egl-43, coordinates G1 cell cycle arrest with pro-invasive gene expression during anchor cell invasion

2019 ◽  
Author(s):  
Ting Deng ◽  
Michael Daube ◽  
Alex Hajnal ◽  
Evelyn Lattmann
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Transcription Factor ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Cell Invasion ◽  
C Elegans ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest ◽  
Anchor Cell

AbstractCell invasion allows cells to migrate across compartment boundaries formed by basement membranes. Aberrant cell invasion is a first step during the formation of metastases by malignant cancer cells.Anchor cell (AC) invasion in C. elegans is an excellent in vivo model to study the regulation of cell invasion during development. Here, we have examined the function of egl-43, the homolog of the human Evi1 proto-oncogene (also called MECOM), in the invading AC. egl-43 plays a dual role in this process, firstly by imposing a G1 cell cycle arrest to prevent AC proliferation, and secondly, by activating pro-invasive gene expression. We have identified the AP-1 transcription factor fos-1 and the Notch homolog lin-12 as critical egl-43 targets. A positive feedback loop between fos-1 and egl-43 induces pro-invasive gene expression in the AC, while repression of lin-12 Notch expression by egl-43 ensures the G1 cell cycle arrest necessary for invasion. Reducing lin-12 levels in egl-43 depleted animals restored the G1 arrest, while hyperactivation of lin-12 signaling in the differentiated AC was sufficient to induce proliferation.Taken together, our data have identified egl-43 Evi1 as a critical factor coordinating cell invasion with cell cycle arrest.Author summaryCells invasion is a fundamental biological process that allows cells to cross compartment boundaries and migrate to new locations. Aberrant cell invasion is a first step during the formation of metastases by malignant cancer cells.We have investigated how a specialized cell in the Nematode C. elegans, the so-called anchor cell, can invade into an adjacent epithelium. Our work has identified an oncogenic transcription factor that controls the expression of specific target genes necessary for cell invasion, and at the same time inhibits the proliferation of the invading anchor cell.These findings shed light on the mechanisms, by which cells decide whether to proliferate or invade.

scholarly journals miR-6734 Up-Regulates p21 Gene Expression and Induces Cell Cycle Arrest and Apoptosis in Colon Cancer Cells

PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0160961 ◽  
Author(s):  
Moo Rim Kang ◽  
Ki Hwan Park ◽  
Jeong-Ook Yang ◽  
Chang Woo Lee ◽  
Soo Jin Oh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Colon Cancer Cells ◽  
Cycle Arrest

scholarly journals Adiponectin differentially affects gene expression in human mammary epithelial and breast cancer cells

2008 ◽  
Vol 99 (8) ◽  
pp. 1246-1250 ◽  
Author(s):  
O Treeck ◽  
C Lattrich ◽  
I Juhasz-Boess ◽  
S Buchholz ◽  
G Pfeiler ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mammary Epithelial ◽  
Human Mammary Epithelial

scholarly journals Detarium microcarpum, Guiera senegalensis, and Cassia siamea Induce Apoptosis and Cell Cycle Arrest and Inhibit Metastasis on MCF7 Breast Cancer Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Ismail Abiola Adebayo ◽  
Haladu Ali Gagman ◽  
Wasiu Gbolahan Balogun ◽  
Mowaffaq Adam Ahmed Adam ◽  
Rafedah Abas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Stem Bark ◽  
Mcf7 Cells ◽  
Cassia Siamea ◽  
Antiproliferative Effects ◽  
Cycle Arrest ◽  
Detarium Microcarpum ◽  
Guiera Senegalensis

Despite the availability of anticancer drugs, breast cancer remains the most death-causing tumor-related disease in women. Hence, there is a need for discovery and development of efficient alternative drugs, and sources such as plants need to be explored. In this study, antioxidant capacities and inhibitory effects against MCF7 cells of the extracts of stem bark of three Nigerian medicinal plants (Detarium microcarpum, Guiera senegalensis, and Cassia siamea) were investigated. The D. microcarpum extracts had the highest antioxidant and antiproliferative effects, followed by that of G. senegalensis, and the C. siamea extracts had minimal effects. The IC50 values of the methanol and aqueous extracts from the three plants that inhibited the proliferation of MCF7 cells ranged from 78–> 500 μg/ml. Moreover, all the plant extracts but the aqueous extract of Cassia siamea exhibited antimetastatic action and induced apoptosis and cell cycle arrest in MCF7 cells. Liquid chromatography/time-of-flight/mass spectrometry profiling revealed that the five potent extracts contain many phenols and omega-6 fatty acids, and some of the identified compounds (isorhamnetin, eupatorin, alpinumisoflavone, procyanidin B3, syringin, and gallic acid) have been reported to have antiproliferative effects on cancer cells. Hence, the stem bark of these plants could be potential sources of antibreast cancer agents.

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