Resveratrol enhances the efficacy of sorafenib mediated apoptosis in human breast cancer MCF7 cells through ROS, cell cycle inhibition, caspase 3 and PARP cleavage

Breast cancer is considered the most common and deadly cancer among women worldwide. Nanomedicine has become extremely attractive in the field of cancer treatment. Due to the high surface to volume ratio and other unique properties, nanomaterials can be specifically targeted to certain cells and tissues to interact with the living systems. The strategic planning of this study is based on using the nanoprecipitation method to prepare nanoparticles BZP-NPs (3.8–5.7 nm) of the previously prepared benzofuran–pyrazole compound (IV) BZP which showed promising cytotoxic activity. The capacity of BZP and BZP-NPs to suppress the growth of human breast tumor MCF-7 and MDA-MB-231 cells was evaluated using MTT assay. The IC50 doses of BZP and BZP-NPs targeting normal breast cells MCF-12A exceeded those targeting the cancer cells by >1000-fold, demonstrating their reasonable safety profiles in normal cells. Furthermore, cell cycle analysis, apoptosis induction detection, assessment of p53, Bcl-2, caspase-3, and PARP-1 levels of BZP and its nano-sized-BZP-NPs particles were also evaluated. Although the obtained results were in the favor of compound IV in its normal-sized particles, BZP-NPs appeared as a hit compound which showed improved cytotoxicity against the tested human breast cancer cells associated with the induction of pre-G1 apoptosis as well as cell cycle arrest at G2/M phase. The increase in caspase-3 level, upregulation of p53, and downregulation of Bcl-2 protein expression levels confirmed apoptosis. Furthermore, ELISA results exhibited that BZP-NPs produced a more favorable impact as a PARP-1 enzyme inhibitor than the parent BZP.

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Cytotoxic activity, apoptosis induction and cell cycle arrest in human breast cancer (MCF7) cells by a novel fluorinated tetrahydro-[1,2,4]triazolo[3,4-a]isoquinolin chalcones

10.21203/rs.3.rs-496965/v1 ◽

2021 ◽

Author(s):

Magda F. Mohamed ◽

Nada S. Ibrahim ◽

Sherif Abdelaziz Ibrahim ◽

May A El-Manawaty ◽

Salwa M. El-Hallouty ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cytotoxic Activity ◽

Mrna Expression ◽

Cancer Cell ◽

Human Breast Cancer ◽

Human Breast ◽

Mcf7 Cells ◽

Cycle Arrest ◽

Mrna Expression Levels

Abstract A series of halogenated chalcones (3–8) was synthesized and confirmed by several spectral tools. The cytotoxic effect of this series was tested against a panel of different cancer cell lines (MCF7, A549, HCT116, and PC3). Our MTT assay results revealed that chalcone 8 had the potent cytotoxic activity against all tested cancer cell lines except A549 cells, which were more sensitive to chalcone 7 relative to the positive control treated with doxorubicin. Chalcone 8 showed the least cytotoxic activity against the normal epithelial cell line RPE-1 and the lowest IC50 at 10.96 µM relative to the IC50 of the chemotherapeutic drug doxorubicin at 12.8 µM against the human breast cancer cell line MCF7. Molecular docking studies showed a good interaction of chalcone 8 with the active site of histone demethylase (PLU-1/ JARID1B) and Carboxy-terminal binding protein1 (CtBP1) proteins. Mechanistically, chalcone 8 induced cell cycle arrest at G2/M phase and apoptosis as assessed by flow cytometry, as well as DNA fragmentation in MCF7 cells. Chalcone 8 upregulated mRNA expression levels of the apoptotic genes BAX, p53, and Caspase-7, Caspase-8, and Caspase-9, whereas mRNA expression levels of the antiapoptotic gene Bcl2, metastasis-related gene matrix metalloproteinase 1, and the autophagic markers ATG5 and LC3B were downregulated as quantified by qPCR.

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Quercetin-induced apoptosis acts through mitochondrial- and caspase-3-dependent pathways in human breast cancer MDA-MB-231 cells

Human & Experimental Toxicology ◽

10.1177/0960327109107002 ◽

2009 ◽

Vol 28 (8) ◽

pp. 493-503 ◽

Cited By ~ 121

Author(s):

Su-Yu Chien ◽

Yao-Chung Wu ◽

Jing-Gung Chung ◽

Jai-Sing Yang ◽

Hsu-Feng Lu ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Viability ◽

Cell Cycle Arrest ◽

Human Breast Cancer ◽

Caspase 3 ◽

Human Breast ◽

Cycle Arrest ◽

Apoptotic Protein ◽

Induced Apoptosis

There has been considerable evidence recently demonstrating the anti-tumour effects of flavonols. Quercetin, an ubiquitous bioactive flavonol, inhibits cells proliferation, induces cell cycle arrest and apoptosis in different cancer cell types. The precise molecular mechanism of quercetin-induced apoptosis in human breast cancer cells is unclear. The purpose of this study was to investigate effects of quercetin on cell viability and to determine its underlying mechanism in human breast cancer MDA-MB-231 cells. Quercetin decreased the percentage of viable cells in a dose- and time-dependent manner, which was associated with cell cycle arrest and apoptosis. Quercetin did not increase reactive oxygen species generation but increased cytosolic Ca2+ levels and reduced the mitochondrial membrane potential (ΔΨm). Quercetin treatment promoted activation of caspase-3, -8 and -9 in MDA-MB-231 cells. Caspase inhibitors prevented the quercetin-induced loss of cell viability. Quercetin increased abundance of the pro-apoptotic protein Bax and decreased the levels of anti-apoptotic protein Bcl-2. Confocal laser microscope examination indicated that quercetin promoted apoptosis-inducing factor (AIF) release from mitochondria and stimulated translocation to the nucleus. Taken together, these findings suggest that quercetin results in human breast cancer MDA-MB-231 cell death through mitochondrial- and caspase-3-dependent pathways.

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Apoptosis induction and cell cycle alterations by extract of Pistacia atlantica (Baneh) in comparison to tamoxifen in human breast cancer T47D cells

Planta Medica ◽

10.1055/s-2007-987308 ◽

2007 ◽

Vol 73 (09) ◽

Author(s):

YY Kamrani ◽

S Fouladdel ◽

T Asgari ◽

G Amin ◽

B Esmaeelian ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Human Breast Cancer ◽

Apoptosis Induction ◽

Human Breast ◽

T47d Cells ◽

Pistacia Atlantica ◽

Cell Cycle Alterations

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Differential Regulation of Cell Cycle Progression in Human Breast Cancer Cell Lines by the Estrogen Receptor

10.21236/ada394036 ◽

2000 ◽

Author(s):

James Direnzo ◽

Myles Brown

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Human Breast Cancer ◽

Cell Cycle Progression ◽

Differential Regulation ◽

Human Breast Cancer Cell ◽

Breast Cancer Cell Lines ◽

Human Breast ◽

Cycle Progression ◽

Regulation Of Cell Cycle

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Molecular Mechanisms of Thymoquinone as Anticancer agent

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323999201027225305 ◽

2020 ◽

Vol 23 ◽

Author(s):

Fatma Ismail Alhmied ◽

Ali Hassan Alammar ◽

Bayan Mohammed Alsultan ◽

Marooj Alshehri ◽

Faheem Hyder Pottoo

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Human Breast Cancer ◽

Phase Cell ◽

Cycle Phase ◽

Human Breast ◽

Cycle Arrest ◽

Phase Arrest ◽

Anti Cancer

Abstract:: Thymoquinone (TQ), the bioactive constituent of Nigella Sativa seeds is a well-known natural compound for the management of several types of cancers. The anti-cancer properties of thymoquinone are thought to be operated via intervening with various oncogenic pathways including cell cycle arrest, prevention of inflammation and oxidative stress, induction of invasion, metastasis, inhibition of angiogenesis, and apoptosis. As well as up-regulation and down-regulation of specific tumor suppressor genes and tumor promoting genes, respectively. Proliferation of various tumor cells is inhibited by TQ via induction of cell cycle arrest, disruption of the microtubule organization, and down regulating cell survival protein expression. TQ induces G1 phase cell cycle arrest in human breast cancer, colon cancer and osteosarcoma cells through inhibiting the activation of cyclin E or cyclin D and up-regulating p27and p21 a cyclin dependent kinase (Cdk) inhibitor. TQ concentration is a significant factor in targeting a particular cell cycle phase. While high concentration of TQ induced G2 phase arrest in human breast cancer (MCF-7) cells, low concentration causes S phase arrest. This review article provides mechanistic insights into the anti-cancer properties of thymoquinone.

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