Mapping Metabolic Events in the Cancer Cell Cycle Reveals Arginine Catabolism in the Committed SG 2M Phase

2018 ◽  
Author(s):  
Irena Roci ◽  
Jeramie D. Watrous ◽  
Kim A. Lagerborg ◽  
Lorenzo Lafranchi ◽  
Arne Lindqvist ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cancer Cell ◽  
Arginine Catabolism ◽  
M Phase

scholarly journals Synthesis and Biological Evaluation of Benzodioxole Derivatives as Potential Anticancer and Antioxidant agents

2020 ◽  
Vol 26 (1) ◽  
pp. 157-167
Author(s):  
Mohammed Hawash ◽  
Ahmad M Eid ◽  
Nidal Jaradat ◽  
Murad Abualhasan ◽  
Johnny Amer ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Anticancer Activity ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Biological Evaluation ◽  
Antioxidant Agents ◽  
M Phase ◽  
Benzodiazepine Derivatives ◽  
Antioxidant Agent ◽  
Synthesis And Biological Evaluation

Abstracta series of benzodioxole compounds were synthesized and evaluated for their cytotoxic activity against cervical (Hela), colorectal (Caco-2), and liver (Hep3B) cancer cell lines. Compounds 5a, 5b, 6a, 6b, 7a and 7b showed very weak or negligible anticancer activity with IC50 3.94-9.12 mM. On the contrary, carboxamide containing compounds 2a and 2b showed anticancer activity. Both 2a and 2b reduced Hep3B secretions of α-fetoprotein (α-FP) to 1625.8 ng/ml and 2340 ng/ml, respectively, compared to 2519.17 ng/ml in untreated cells. The results also showed that compound 2a has potent anticancer activity against Hep3B cancer cell line. Furthermore, in cell cycle analysis, compound 2a induced arrest in the G2-M phase in value of 8.07% that was very close to the activity of doxorubicin (7.4%). These results indicate that compound 2a has a potent and promising antitumor activity. However, benzodiazepine derivatives (7a and 7b) showed moderate antioxidant activity with IC50 values of 39.85 and 79.95 μM, respectively compared with the potent antioxidant agent Trolox (IC50 = 7.72 μM).

scholarly journals Synthesis of 2,6-Diamino-Substituted Purine Derivatives and Evaluation of Cell Cycle Arrest in Breast and Colorectal Cancer Cells

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 1996 ◽  
Author(s):  
Bartolomeo Bosco ◽  
Andrea Defant ◽  
Andrea Messina ◽  
Tania Incitti ◽  
Denise Sighel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Density Functional ◽  
Cell Cycle Progression ◽  
Cycle Arrest ◽  
M Phase

Reversine is a potent antitumor 2,6-diamino-substituted purine acting as an Aurora kinases inhibitor and interfering with cancer cell cycle progression. In this study we describe three reversine-related molecules, designed by docking calculation, that present structural modifications in the diamino units at positions 2 and 6. We investigated the conformations of the most stable prototropic tautomers of one of these molecules, the N6-cyclohexyl-N6-methyl-N2-phenyl-7H-purine-2,6-diamine (3), by Density Functional Theory (DFT) calculation in the gas phase, water and chloroform, the last solvent considered to give insights into the detection of broad signals in NMR analysis. In all cases the HN(9) tautomer resulted more stable than the HN(7) form, but the most stable conformations changed in different solvents. Molecules 1–3 were evaluated on MCF-7 breast and HCT116 colorectal cancer cell lines showing that, while being less cytotoxic than reversine, they still caused cell cycle arrest in G2/M phase and polyploidy. Unlike reversine, which produced a pronounced cell cycle arrest in G2/M phase in all the cell lines used, similar concentrations of 1–3 were effective only in cells where p53 was deleted or down-regulated. Therefore, our findings support a potential selective role of these structurally simplified, reversine-related molecules in p53-defective cancer cells.

scholarly journals Co-treatment of Brazilein Enhances Cytotoxicity of Doxorubicin on WiDr Colorectal Cancer Cells Through Cell Cycle Arrest

2020 ◽  
Vol 12 (4) ◽  
pp. 376-383
Author(s):  
Diah Tri Utami ◽  
Nadzifa Nugraheni ◽  
Riris Istighfari Jenie ◽  
Edy Meiyanto
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Synergistic Effect ◽  
Cell Cycle Arrest ◽  
Cancer Cell ◽  
Combination Index ◽  
Cancer Cell Line ◽  
Chemotherapeutic Agents ◽  
Cycle Arrest ◽  
M Phase

BACKGROUND: The presence of adverse side effects limits the use of doxorubicin (Dox) despite its cost-effectiveness compared to other chemotherapeutic agents. Brazilein (Be), the major compound of Caesalpinia sappan, performs co-chemotherapeutic potency in several cancer cell lines. This study evaluates the chemosensitizing effects of Be to Dox on colon cancer cell line, WiDr.METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was conducted to evaluate the cytotoxic effect of Be and its combination with Dox. The synergistic effect of Be and Dox was examined by using the Combination index (CI) parameter. Cell cycle and apoptosis profiles were done using flow cytometry with propidium iodide (PI)/RNase and Annexin V staining, respectively.RESULTS: The combination of Dox and Be at half of IC50 on WiDr cells showed a synergistic effect with a combination index of 0.4. Analysis of the cell cycle revealed that the combination caused cell cycle termination at the S and G2/M phase. This finding corresponded with the data that single treatment of Dox and Be induced cell cycle arrest at the different phases, namely S and G2/M phase, respectively. However, the combination treatment for 24 hours did not induce apoptosis. This combination should be further clarified as there was a possibility that many cells may underwent permanently arrest that halts to proceed apoptosis.CONCLUSION: Our findings suggested that Be synergizes with Dox to suppress the growth of WiDr cells via cell cycle arrest, hence, Be is potential to be developed as a co-chemotherapeutic agent. Our findings suggested that Be synergizes with Dox to suppress the growth of WiDr cells via cell cycle arrest, hence, Be is potential to be developed as a co-chemotherapeutic agent.KEYWORDS: Brazilein, colon cancer WiDr, co-treatment, Doxorubicin, cell cycle arrest

Comparison of traditional Chinese medicine (TCM) herbal mixture LQ and paclitaxel on the phase of cancer cell cycle blockage and cancer cell invasion.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22014-e22014
Author(s):  
Robert M. Hoffman ◽  
Chengyu Wu ◽  
Shuya Yano ◽  
Lei Zhang
Keyword(s):  
Cell Cycle ◽  
Cancer Cell ◽  
Hela Cells ◽  
Positive Control ◽  
Control Group ◽  
Herbal Mixture ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
M Phase ◽  
Treated Culture

e22014 Background: Although Traditional Chinese Medicine (TCM) has been used to treat cancer for thousands of years, the mechanisms of action are either poorly understood or unknown. In the present report, we use state-of-the-art technology to investigate the anti-cancer mechanism of the TCM herbal mixture LQ. Methods: Fluorescence ubiquitination-based cell cycle indicator (FUCCI) was used to monitor cell cycle arrest HeLa cells after LQ treatment. FUCCI-HeLa cells were cultured in two dimensional (2D) monolayer, Matrigel and 3D Gelfoam. Changes of cell cycle status were observed using the Olympus FV1000 confocal imaging system whereby cycling cells fluoresce green and quiescent cells red. Paclitaxel (Taxol) was used as the positive control. Results: Paclitaxel induced a G2/M cell cycle block. In contrast, LQ blocked FUCCI-HeLa cells in the G0/G1 phase of the cell cycle in all 3 culture models. In monolayer culture, the paclitaxel positive control had approximately 45% of the cells in G2/M phase. In contrast, the LQ-treated cells were mostly in the G0/G1 phase (>90%). In Matrigel culture, HeLa cells formed spheres. The spheres in the paclitaxel control group had 40% of the cells in G2/M phase, but only 15% in LQ-treated cultures. In 3D Gelfoam culture, cells grew along the structures of the Gelform. The paclitaxel positive control culture had approximately 45% of cells in G2/M phase. In contrast, the cells in LQ-treated culture were mostly in G0/G1 phase (>80%). The cells in pacilitaxel control group invaded to 250~300 µm deep in the Gelfoam, but only 150~200 µm deep in LQ-treated culture. Conclusions: The anti-cancer mechanism of TCM herbal mixture LQ involves cancer cell cycle arrest at G0/G1 and inhibition of cancer cell invasion.

scholarly journals Mapping Metabolic Events in the Cancer Cell Cycle Reveals Arginine Catabolism in the Committed SG2M Phase

Cell Reports ◽  
2019 ◽  
Vol 26 (7) ◽  
pp. 1691-1700.e5 ◽  
Author(s):  
Irena Roci ◽  
Jeramie D. Watrous ◽  
Kim A. Lagerborg ◽  
Lorenzo Lafranchi ◽  
Arne Lindqvist ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cancer Cell ◽  
Arginine Catabolism

scholarly journals miR-210 regulates esophageal cancer cell proliferation by inducing G2/M phase cell cycle arrest through targeting PLK1

2014 ◽  
Vol 10 (4) ◽  
pp. 2099-2104 ◽  
Author(s):  
CHENGLIN LI ◽  
XINLIANG ZHOU ◽  
YADI WANG ◽  
SHAOWU JING ◽  
CONGRONG YANG ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Esophageal Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cell ◽  
Phase Cell ◽  
Cancer Cell Proliferation ◽  
Cycle Arrest ◽  
M Phase ◽  
Esophageal Cancer Cell

scholarly journals Phenolic Compounds Isolated from Caesalpinia coriaria Induce S and G2/M Phase Cell Cycle Arrest Differentially and Trigger Cell Death by Interfering with Microtubule Dynamics in Cancer Cell Lines

Molecules ◽  
2017 ◽  
Vol 22 (4) ◽  
pp. 666 ◽  
Author(s):  
Jessica Sánchez-Carranza ◽  
Laura Alvarez ◽  
Silvia Marquina-Bahena ◽  
Enrique Salas-Vidal ◽  
Verónica Cuevas ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Phenolic Compounds ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Cancer Cell ◽  
Phase Cell ◽  
Cycle Arrest ◽  
M Phase ◽  
Trigger Cell Death

2, 4, 5-Trideoxyhexopyranosides Derivatives of 4’- Demethylepipodophyllotoxin: De novo Synthesis and Anticancer Activity

2020 ◽  
Vol 16 ◽  
Author(s):  
Yapeng Lu ◽  
Li Zhu ◽  
Rui Cai ◽  
Yu Li ◽  
Yu Zhao
Keyword(s):  
Cell Cycle ◽  
Cancer Cell ◽  
De Novo ◽  
Building Blocks ◽  
Dependent Manner ◽  
De Novo Synthesis ◽  
Concentration Dependent Manner ◽  
Cycle Arrest ◽  
M Phase ◽  
Derivatives Of

Background: Podophyllotoxin is a natural lignan which possesses anticancer and antiviral activities. Etoposide and teniposide are semisynthetic glycoside derivatives of podophyllotoxin and are increasingly used in cancer medicine. Objective: The present work was aimed to design and synthesize a series of 2, 4, 5-trideoxyhexopyranosides derivatives of 4’-demethylepipodophyllotoxin as novel anticancer agents. Methods: A divergent de novo synthesis of 2, 4, 5-trideoxyhexopyranosides derivatives of 4’-demethylepipodophyllotoxin has been established via palladium-catalyzed glycosylation. The abilities of synthesized glycosides to inhibit the growth of A549, HepG2, SH-SY5Y, KB/VCR and HeLa cancer cells were investigated by MTT assay. Flow cytometric analysis of cell cycle with propidium iodide DNA staining was employed to observe the effect of compound 5b on cancer cell cycle. Results: Twelve D and L monosaccharides derivatives 5a-5l have been efficiently synthesized in three steps from various pyranone building blocks employing de novo glycosylation strategy. D-monosaccharide 5b showed highest cytotoxicity on five cancer cell lines with the IC50 values from 0.9 to 6.7 mM. It caused HepG2 cycle arrest at G2/M phase in a concentration-dependent manner. Conclusion: The present work leads to the development of novel 2, 4, 5-trideoxyhexopyranosides derivatives of 4’- demethylepipodophyllotoxin. The biological results suggested that the replacement of the glucosyl moiety of etoposide with 2, 4, 5-trideoxyhexopyranosyl is favorable to their cytotoxicity. D-monosaccharide 5b caused HepG2 cycle arrest at G2/M phase in a concentration-dependent manner.

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