scholarly journals Novel flavonoids as anti-cancer agents: mechanisms of action and promise for their potential application in breast cancer

2014 ◽  
Vol 42 (4) ◽  
pp. 1017-1023 ◽  
Author(s):  
Carlos Martinez-Perez ◽  
Carol Ward ◽  
Graeme Cook ◽  
Peter Mullen ◽  
Donald McPhail ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Potential Application ◽  
Great Promise ◽  
Effective Mechanism ◽  
Cycle Arrest ◽  
Antioxidant Agents ◽  
Wide Range ◽  
Anti Cancer ◽  
Oestrogen Signalling ◽  
Anti Tumour Effect

Flavonoids are a large group of ubiquitous polyphenolic secondary metabolites in plants with a wide range of properties, including a widely reported anti-cancer effect. The present review focuses on the different known mechanisms partaking in said anti-tumour effects, with particular emphasis on breast cancer. Their structure and reactivity allows flavonoids to work as antioxidant agents and phyto-oestrogens, modulating oestrogen signalling and metabolism to induce an overall anti-proliferative response. Other effects include the ability of flavonoids to modulate the CYP1 (cytochrome P450 1) and ABC (ATP-binding cassette) protein families, involved in carcinogenesis and drug delivery respectively. They can also induce apoptosis and cell cycle arrest and regulate other signalling pathways involved in the development and progression of cancer. In conclusion, there is accumulating evidence on the versatility of flavonoids and the numerous activities contributing to their anti-tumour effect. The complex, yet effective, mechanism of action of flavonoids, together with their interesting pharmacological properties, is the basis for their potential application in breast and other cancers. This rationale has led to the current interest in the application of flavonoids, including clinical trials currently underway and the development of novel flavonoids with improved properties, which hold great promise for tackling breast cancer.

Molecular Mechanisms of Thymoquinone as Anticancer agent

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.

scholarly journals Differential Mechanisms of Cell Death Induced by HDAC Inhibitor SAHA and MDM2 Inhibitor RG7388 in MCF-7 Cells

Cells ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 8 ◽  
Author(s):  
Umamaheswari Natarajan ◽  
Thiagarajan Venkatesan ◽  
Vijayaraghavan Radhakrishnan ◽  
Shila Samuel ◽  
Appu Rathinavelu
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Cancer Cells ◽  
Hdac Inhibitor ◽  
The Other ◽  
Combination Treatments ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Mcf 7

Gene expression is often altered by epigenetic modifications that can significantly influence the growth ability and progression of cancers. SAHA (Suberoylanilide hydroxamic acid, also known as Vorinostat), a well-known Histone deacetylase (HDAC) inhibitor, can stop cancer growth and metastatic processes through epigenetic alterations. On the other hand, Letrozole is an aromatase inhibitor that can elicit strong anti-cancer effects on breast cancer through direct and indirect mechanisms. A newly developed inhibitor, RG7388 specific for an oncogene-derived protein called MDM2, is in clinical trials for the treatment of various cancers. In this paper, we performed assays to measure the effects of cell cycle arrest resulting from individual drug treatments or combination treatments with SAHA + letrozole and SAHA + RG7388, using the MCF-7 breast cancer cells. When SAHA was used individually, or in combination treatments with RG7388, a significant increase in the cytotoxic effect was obtained. Induction of cell cycle arrest by SAHA in cancer cells was evidenced by elevated p21 protein levels. In addition, SAHA treatment in MCF-7 cells showed significant up-regulation in phospho-RIP3 and MLKL levels. Our results confirmed that cell death caused by SAHA treatment was primarily through the induction of necroptosis. On the other hand, the RG7388 treatment was able to induce apoptosis by elevating BAX levels. It appears that, during combination treatments, with SAHA and RG7388, two parallel pathways might be induced simultaneously, that could lead to increased cancer cell death. SAHA appears to induce cell necroptosis in a p21-dependent manner, and RG7388 seems to induce apoptosis in a p21-independent manner, outlining differential mechanisms of cell death induction. However, further studies are needed to fully understand the intracellular mechanisms that are triggered by these two anti-cancer agents.

scholarly journals Stereoselective Anti-Cancer Activities of Ginsenoside Rg3 on Triple Negative Breast Cancer Cell Models

2019 ◽  
Vol 12 (3) ◽  
pp. 117 ◽  
Author(s):  
Nakhjavani ◽  
Palethorpe ◽  
Tomita ◽  
Smith ◽  
Price ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Lines ◽  
Triple Negative ◽  
Migration And Invasion ◽  
Ginsenoside Rg3 ◽  
Cycle Arrest ◽  
Tnbc Cell ◽  
Anti Cancer ◽  
Aqp1 Expression

Ginsenoside Rg3 (Rg3) has two epimers, 20(S)-ginsenoside Rg3 (SRg3) and 20(R)-ginsenoside Rg3 (RRg3), and while Rg3 itself has been reported to have anti-cancer properties, few studies have been reported on the anti-cancer effects of the different epimers. The aim was to investigate the stereoselective effects of the Rg3 epimers on triple negative breast cancer (TNBC) cell lines, tested using cell-based assays for proliferation, apoptosis, cell cycle arrest, migration and invasion. Molecular docking showed that Rg3 interacted with the aquaporin 1 (AQP1) water channel (binding score −9.4 kJ mol−1). The Xenopus laevis oocyte expression system was used to study the effect of Rg3 epimers on the AQP1 water permeability. The AQP1 expression in TNBC cell lines was compared with quantitative-polymerase chain reaction (PCR). The results showed that only SRg3 inhibited the AQP1 water flux and inhibited the proliferation of MDA-MB-231 (100 μM), due to cell cycle arrest at G0/G1. SRg3 inhibited the chemoattractant-induced migration of MDA-MB-231. The AQP1 expression in MDA-MB-231 was higher than in HCC1143 or DU4475 cell lines. These results suggest a role for AQP1 in the proliferation and chemoattractant-induced migration of this cell line. Compared to SRg3, RRg3 had more potency and efficacy, inhibiting the migration and invasion of MDA-MB-231. Rg3 has stereoselective anti-cancer effects in the AQP1 high-expressing cell line MDA-MB-231.

Anti-cancer effect of Urginea maritima bulb extract invitro through cell cycle arrest and induction of apoptosis in human breast cancer cell lines

2020 ◽  
Vol 17 ◽  
Author(s):  
Khadije Saket ◽  
Roshanak Salari ◽  
Ehsan Saburi ◽  
Mahdi Yousefi ◽  
Mohammad Ali Khodadoust ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Migration ◽  
Cell Cycle Arrest ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Induction Of Apoptosis ◽  
Mcf 7

Background: Breast cancer is the most common known malignancy in women and it is therefore very important to prevent and treat this cancer. In this experimental study, the anti-breast cancer effect of Urginea matrima was investigated. Method: Breast cancer cell lines [MCF-7 and MDA-MB231] and L929 normal cells [as a control group] were cultivated in DMEM medium. Bulb aqueous and hydroalcoholic extracts [70:30] were prepared through maceration method. The cultured cells were treated with different concentrations [6, 3, 1.5, 0.75, 0.375, 0.187 and 0.093 μg/mL] of U.maritima extracts for 24, 48 and 72 h. Toxicity of the extracts on cells were examined using MTT test. The Annexin V–FITC Apoptosis Detection Kit was used to evaluate apoptosis and necrosis. Flow cytometry technique was employed to evaluate the cell cycle and the cell migration was evaluated by Scratch method. Data were analyzed by GraphPad Prism and SPSS software and P <0.05 was considered significant. Result: Results showed that both extracts of U.maritima in the concentration of 1.5 and 3 μg/ ml at 24,48 and 72h presented cytotoxicity effect on MCF7 cell line . Also, both extracts in the concentration of 3 μg/ ml at 24 and 72h, and in the concentration of 6 μg/ ml at 72h showed cytotoxicity effect significantly on MDA-MB231 cells. In addition, the plant extracts at the dosage of 3 and 6 μg/ ml induced an accumulation of G0/G1 cells, as well as reduce in S and G2/M phases in MCF-7 and MDA-MB231 cells. Moreover, the aqueous and hydroalcoholic of U.maritima extracts at three concentrations [ 1.5, 3 and 6 μg/ ml ] in 24h inhibited the cell migration by 60% up to 70% respectively. In addition, the content of phenolic compounds in both extracts [aqueous and hydroalcoholic] was 7 mg and 10 mg gallic acid equivalent per gram of the crude extract, respectively. Conclusion: Our results suggest that U.maritima extracts has significant anti-cancer activity against breast cancer cells due to cell cycle arrest and induction of apoptosis pathway.

scholarly journals Cepharanthine Induces Autophagy, Apoptosis and Cell Cycle Arrest in Breast Cancer Cells

2017 ◽  
Vol 41 (4) ◽  
pp. 1633-1648 ◽  
Author(s):  
Sumei Gao ◽  
Xiaoyan Li ◽  
Xia Ding ◽  
Wenwen Qi ◽  
Qifeng Yang
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Invasion And Migration ◽  
Cycle Arrest ◽  
And Migration ◽  
Anti Tumour Effect

Background: Cepharanthine (CEP) is a biscoclaurine alkaloid extracted from Stephania cepharantha and has been shown to have an anti-tumour effect on different types of cancers. However, the anti-cancer effect of CEP on human breast cancer cells is still unclear. Methods: We used MTT, clone formation, in vitro scratch, invasion and migration assays to confirm the inhibitory role of CEP on the proliferation of breast cancer cells. Flow cytometry, plasmid construction and western blot analysis were used to study the detailed mechanisms. Results: Our study showed that CEP could inhibit cell proliferation by inducing autophagy, apoptosis, and G0/G1 cell cycle arrest of breast cancer cells. Furthermore, we found that CEP induced autophagy and apoptosis by inhibiting the AKT/mTOR signalling pathway. Conclusion: We found that CEP could inhibit growth and motility of MCF-7 and MDA-MB-231 breast cancer cell. Our study revealed an anti-tumour effect of CEP on breast cancer cells and suggests that CEP could be a potential new clinical therapy for breast cancer.

DNA Fragmentation, Cell Cycle Arrest, and Docking Study of Novel Bis Spiro-cyclic 2-oxindole of Pyrimido[4,5-b]quinoline-4,6-dione Derivatives Against Breast Carcinoma

2018 ◽  
Vol 18 (4) ◽  
pp. 372-381 ◽  
Author(s):  
Magda F. Mohamed ◽  
Amr Mohamed Abdelmoniem ◽  
Ahmed H.M. Elwahy ◽  
Ismail A. Abdelhamid
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Anticancer Activity ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
A549 Cell ◽  
Cytotoxic Effect ◽  
Quinoline Derivatives ◽  
Cycle Arrest ◽  
Wide Range

Background: Recently, it is reported that heterocycles containing pyrimidoquinoline moiety show a broad spectrum of medicinal and pharmacological properties including anticancer, anti-microbial, anti-inflammatory activities, analgesic and antiviral. In additions, spirocyclicoxindole containing compounds represent an important class of compounds that exhibit wide range of biological properties. The asymmetric chiral spiro carbon is considered to be the main criteria of the bioactivities. Spirooxindole structures represent the main skeleton for various alkaloids and pharmaceutically important compounds. Among them, the naturally occurring pyrrolidinylespirooxindole alkaloid, horsifiline that exhibits anticancer activity against human brain cancer cell lines. Objective: The objective of this study is the synthesis of novel bis spiro-cyclic 2-oxindole of pyrimido[4,5-b]quinoline derivatives and evaluate the anticancer activity of new compounds for synergistic purpose. Different genetic tools were used in an attempt to know the mechanism of action of this compound against breast cancer. Method: An efficient one pot synthesis of bis spiro-cyclic 2-oxindole derivatives of pyrimido[4,5- b]quinoline-4,6-dione using 6-aminouracil, bis-isatin and dimedone has been developed. The cytotoxic effect against different human cell lines MCF7, HCT116 and A549 cell lines was evaluated. The derivative 6a, was found the most encouraging compound in this series and it was selected for molecular studies against MCF7. Results: Our data indicated that compound 6a is an attractive target for breast cancer, as it inhibits proliferation, cell cycle progression and induces apoptosis of tumor cells. This inhibition is mediated by fragmentation of genomic DNA, up-regulation of [caspase-3, tumor suppressor gene p53, and pro-apoptotic gene BAX], and down-regulation of anti-apoptotic BCL2 gene. In additions it caused cell cycle arrest in S phase. This work provides an evidence of the potent effect of the new compound 6a and assists in the progress of new healing agents for cancer. Conclusion: We have developed an efficient method for the synthesis of novel bioactive bis spirocyclic 2-oxindole derivatives incorporating pyrimido[4,5-b]quinoline derivatives. Most of our new derivatives give potent cytotoxic effect more than the standard drug Fluorouracil (5-FU) especially, compound 6a which was the most active and promising one in this series against MCF7, HCT116, and A549 cell lines.

scholarly journals Palbociclib Induces Senescence in Melanoma and Breast Cancer Cells and Leads to Additive Growth Arrest in Combination With Irradiation

2021 ◽  
Vol 11 ◽  
Author(s):  
Tina Jost ◽  
Lucie Heinzerling ◽  
Rainer Fietkau ◽  
Markus Hecht ◽  
Luitpold V. Distel
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Growth Arrest ◽  
Melanoma Cells ◽  
Cellular Growth ◽  
Cycle Arrest ◽  
Wide Range

IntroductionSeveral kinase inhibitors (KI) bear the potential to act as radiosensitizers. Little is known of the radiosensitizing effects of a wide range of other KI like palbociclib, which is approved in ER+/HER2- metastatic breast cancer.MethodIn our study, we used healthy donor fibroblasts and breast cancer and skin cancer cells to investigate the influence of a concomitant KI + radiation therapy. Cell death and cell cycle distribution were studied by flow cytometry after Annexin-V/7-AAD and Hoechst staining. Cellular growth arrest was studied in colony-forming assays. Furthermore, we used C12-FDG staining (senescence) and mRNA expression analysis (qPCR) to clarify cellular mechanisms.ResultsThe CDK4/6 inhibitor palbociclib induced a cell cycle arrest in the G0/G1 phase. Cellular toxicity (cell death) was only slightly increased by palbociclib and not enhanced by additional radiotherapy. As the main outcome of the colony formation assays, we found that cellular growth arrest was induced by palbociclib and improved by radiotherapy in an additive manner. Noticeably, palbociclib treatment clearly induced senescence not only in breast cancer and partly in melanoma cells, but also in healthy fibroblasts. According to these findings, the downregulation of senescence-related FOXM1 might be an involved mechanism of the senescence-induction potential of palbociclib.ConclusionThe effect on cellular growth arrest of palbociclib and radiotherapy is additive. Palbociclib induces permanent G0/G1 cell cycle arrest by inducing senescence in fibroblasts, breast cancer, and melanoma cells. Direct cell death induction is only a minor secondary mechanism of action. Concomitant KI and radiotherapy is a strategy worth studying in clinical trials.

scholarly journals Detection and Spatiotemporal analysis of in-vitro 3D migratory Triple-Negative Breast cancer cells

2021 ◽  
Author(s):  
Nikolaos M Dimitriou ◽  
Salvador Flores-Torres ◽  
Joseph Matthew Kinsella ◽  
Georgios D Mitsis
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Spatial Organization ◽  
Triple Negative ◽  
Migration And Invasion ◽  
Great Promise ◽  
Cell Nuclei ◽  
Wide Range

The invasion of cancer cells into the surrounding tissues is one of the hallmarks of cancer. However, a precise quantitative understanding of the spatiotemporal patterns of cancer cell migration and invasion still remains elusive. A promising approach to investigate these patterns are 3D cell cultures, which provide more realistic models of cancer growth compared to conventional 2D monolayers. Quantifying the spatial distribution of cells in these 3D cultures yields great promise for understanding the spatiotemporal progression of cancer. In the present study, we present an image processing and segmentation pipeline for the detection of 3D GFP-fluorescent Triple-Negative Breast Cancer cell nuclei, and we perform quantitative analysis of the formed spatial patterns and their temporal evolution. The performance of the proposed pipeline was evaluated using experimental 3D cell culture data, and was found to be comparable to manual segmentation, outperforming four alternative automated methods. The spatiotemporal statistical analysis of the detected distributions of nuclei revealed transient, non-random spatial distributions that consisted of clustered patterns across a wide range of neighbourhood distances, as well as dispersion for larger distances. Overall, the implementation of the proposed framework revealed the spatial organization of cellular nuclei with improved accuracy, providing insights into the 3 dimensional inter-cellular organization and its progression through time.

scholarly journals Evaluation of Anticancer Activity of Neolamarckia Cadamba Leaves and Its Metabolite Profile

2021 ◽  
Author(s):  
Shakirah Razali ◽  
Al’aina Firus Khan ◽  
Alfi Khatib ◽  
Qamar Uddin Ahmed ◽  
Habibah Hassan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Traditional Use ◽  
Chromatography Analysis ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Mcf 7

Abstract Neolamarckia cadamba (NC) leaf is traditionally used for the treatment of breast cancer, however this claim is unverified. This study aimed to evaluate the anti-cancer activities of NC leaf ethanol extract on breast cancer cell line (MCF-7 cells) using in vitro cell viability, cytotoxicity and gene expression assays followed by gas chromatography analysis. Results revealed inhibition concentration (IC50) against MCF-7 at 0.2 mg/mL. The extract exerted a dose and time dependent inhibitory effect against MCF-7 cells. The cell cycle assay showed that the extract arrested MCF-7 cells in G0/G1 phase, and apoptosis were observed after 72 hours by Annexin-V assay. The gene expression assay revealed that the cell cycle arrest was associated with the down-regulation of CDK2 and subsequent up-regulation of p21 and cyclin E. The extract induced apoptosis via mediation of the mitochondrial cell death pathways. Chromatography analysis revealed the contribution of d-pinitol and myo-inositol to the activity observed as the two major bioactive compounds. Overall, the study demonstrated that NC exerts anti-cancer effect on MCF-7 human breast cancer cells through induction of apoptosis and cell cycle arrest thus justifying its traditional use for breast cancer treatment in Malaysia.

scholarly journals Study of antioxidant activity of selected monocarbohydrazone derivatives

2021 ◽  
Vol 62 (1) ◽  
pp. 5-8
Author(s):  
Gorana Mrđan ◽  
Borko Matijević ◽  
Sanja Vlaisavljević ◽  
Đenđi Vaštag ◽  
Suzana Apostolov
Keyword(s):  
Sulfonic Acid ◽  
Biological Activities ◽  
Biologically Active ◽  
Radical Scavengers ◽  
Antioxidant Power ◽  
Antioxidant Agents ◽  
Wide Range ◽  
Anti Cancer ◽  
Ferric Reducing Antioxidant Power ◽  
Active Substances

Many of carbohydrazone derivatives have shown a wide range of biological activities. In previous studies, these compounds have proven to be excellent anti-cancer, antitumor, antibacterial, antimicrobial and antioxidant agents. Monocarbohydrazones, as one of the carbohydrazone derivatives, have been slightly explored. Due to that reason, in this study, eight newly synthesized monocarbohydrazones were subjected to examinations by the use of three antioxidant tests. To determine the effectiveness of monocarbohydrazone as potential radical scavengers, DPPH (2,2-Diphenyl-1-picrylhydrazyl), ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) and FRAP (Ferric Reducing Antioxidant Power) assays were used. The obtained results could open the door for further studies of these compounds as biologically active substances.

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