scholarly journals Effect of Aspirin on Cell Growth of Human MG-63 Osteosarcoma Line

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
E. De Luna-Bertos ◽  
J. Ramos-Torrecillas ◽  
O. García-Martínez ◽  
L. Díaz-Rodríguez ◽  
C. Ruiz

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in bone tissue repair treatment for their pharmacological action. The objective of this study was to determine the effect of aspirin, on osteoblast growth, using MG63 cell line as osteoblast model. MTT spectrophotometry results showed that 20, 100, and 1000 μM aspirin doses have an inhibitory effect on growth. Cell cycle analysis revealed that aspirin doses of 100 and 1000 μM arrest the cell cycle in phase GO/G1. Parallel apoptosis/necrosis studies showed no changes in comparison to control cells after treatment with 1 or 10 μM aspirin but a significantly increased percentage of cells in apoptosis at doses of 20, 100, and 1000 μM. We highlight that treatment of osteoblast-like cells with 1000 μM aspirin increased not only the percentage of cells in apoptosis but also the percentage of necrotic cells, which was not observed in aspirin treatments at lower doses.

2014 ◽  
Vol 17 (1) ◽  
pp. 62-67 ◽  
Author(s):  
Elvira De Luna-Bertos ◽  
Javier Ramos-Torrecillas ◽  
Francisco Javier Manzano-Moreno ◽  
Olga García-Martínez ◽  
Concepción Ruiz

Some nonsteroidal anti-inflammatory drugs (NSAIDs) have adverse effects on bone tissue. The objective of this study was to determine the effect of different doses of dexketoprofen, ketorolac, and metamizole on growth of the osteoblast MG63 cell line. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide spectrophotometry results showed that MG63 cell growth was significantly inhibited after 24 hr of culture with doses of 10, 20, 100, or 1,000 µM of each NSAID and with doses of 0.1, 1, or 5 µM of dexketoprofen and ketorolac but not metamizole. Cell-cycle studies revealed that dexketoprofen and ketorolac treatments significantly arrested the cell cycle in phase G0/G1, increasing the percentage of cells in this phase. Apoptosis/necrosis studies showed significant changes versus control cells, with an increased percentage of cells in apoptosis after treatment with 10, 100, or 1,000 µM of metamizole and after treatment with 1, 10, 100, or 1,000 µM of dexketoprofen or ketorolac. In conclusion, treatment of osteoblast-like cells with high doses of the NSAIDs tested increased not only the percentage of cells in apoptosis but also the percentage of necrotic cells.


2021 ◽  
pp. 1-10
Author(s):  
Sandra Appiah ◽  
Cynthia. U. Osemeke ◽  
Xuesong Wen ◽  
Hemda Garelick ◽  
Sandra Appiah

Acute myeloid leukemia (AML) is associated with numerous mutations, with the Feline McDonough Sarcoma (FMS) like tyrosine kinase 3 (FLT3) mutation resulting in with poor prognosis and outcome. Therapies have been developed using FLT3 inhibitors, however, drug resistance often leads to disease relapse. In this study, α-Mangostin and doxorubicin (Dox) were evaluated, singly and in combination, for their anti-leukemic effect on MOLM-13, an AML cell line with FLT3-ITD mutation. Cell viability and apoptosis were determined using CyQUANTGR and TUNEL assay, respectively. Cell cycle analysis was conducted on propidium iodide-stained cells using flow cytometry. Cellular proteins were quantified using Western blot technique, with additional study by ELISA for FLT3 kinase activity. The results revealed that cell treatment by the combined drug, Dox (1 µM) and α-Mangostin (20 µM), compared to Dox (1 µM) alone, caused a significant inhibitory effect (P<0.001) and indicated synergistic cell growth inhibition. The combined drug also showed increased TUNEL positive apoptotic cells and increased expression of the pro-apoptotic protein Bak compared to Dox alone (P<0.05). Dox treated cells, as well as the combined drug induced cell cycle arrest at G2/M phase compared to untreated cells (P<0.05 and P<0.001, respectively). There was also statistically significant (P<0.05) reduction of cdc25 phosphatases (enzymes which play an important role in G2/M transition) by the combination drug compared to sole cell treatment by Dox. Furthermore, phosphorylated FLT3 protein expression was reduced when the combined treatment was compared to Dox only after 2 h (P<0.05) and after 24 h (P<0.001). Thus, Dox and α-Mangostin combined treatment inhibited FLT3 phosphorylation in MOLM-13 cells which could have contributed to G2M cell arrest and apoptosis via cdc25s and Bak proteins respectively. Further studies are warranted to further evaluate the potential of Dox and α-Mangostin combined drug as inhibitors of FLT3-ITD phosphorylation and its potential clinical relevance in AML treatment.


2020 ◽  
Vol 16 ◽  
Author(s):  
Jamshed Iqbal ◽  
Ayesha Basharat ◽  
Sehrish Bano ◽  
Syed Mobasher Ali Abid ◽  
Julie Pelletier ◽  
...  

Aims: The present study was conducted to examine the inhibitory effects of synthesized sulfonylhydrazones on the expression of CD73 (ecto-5′-NT). Background: CD73 (ecto-5′-NT) represents the most significant class of ecto-nucleotidases which are mainly responsible for dephosphorylation of adenosine monophosphate to adenosine. Inhibition of CD73 played an important role in the treatment of cancer, autoimmune disorders, precancerous syndromes, and some other diseases associated with CD73 activity. Objective: Keeping in view the significance of CD73 inhibitor in the treatment of cervical cancer, a series of sulfonylhydrazones (3a-3i) derivatives synthesized from 3-formylchromones were evaluated. Methods: All sulfonylhydrazones (3a-3i) were evaluated for their inhibitory activity towards CD73 (ecto-5′-NT) by the malachite green assay and their cytotoxic effect was investigated on HeLa cell line using MTT assay. Secondly, most potent compound was selected for cell apoptosis, immunofluorescence staining and cell cycle analysis. After that, CD73 mRNA and protein expression were analyzed by real-time PCR and Western blot. Results: Among all compounds, 3h, 3e, 3b, and 3c were found the most active against rat-ecto-5′-NT (CD73) enzyme with IC50 (µM) values of 0.70 ± 0.06 µM, 0.87 ± 0.05 µM, 0.39 ± 0.02 µM and 0.33 ± 0.03 µM, respectively. These derivatives were further evaluated for their cytotoxic potential against cancer cell line (HeLa). Compound 3h and 3c showed the cytotoxicity at IC50 value of 30.20 ± 3.11 µM and 86.02 ± 7.11 µM, respectively. Furthermore, compound 3h was selected for cell apoptosis, immunofluorescence staining and cell cycle analysis which showed promising apoptotic effect in HeLa cells. Additionally, compound 3h was further investigated for its effect on expression of CD73 using qRT-PCR and western blot. Conclusion: Among all synthesized compounds (3a-3i), Compound 3h (E)-N'-((6-ethyl-4-oxo-4H-chromen-3-yl) methylene)-4-methylbenzenesulfonohydrazide was identified as most potent compound. Additional expression studies conducted on HeLa cell line proved that this compound successfully decreased the expression level of CD73 and thus inhibiting the growth and proliferation of cancer cells.


2019 ◽  
Vol 18 (11) ◽  
pp. 1551-1562 ◽  
Author(s):  
Abbas Kabir ◽  
Kalpana Tilekar ◽  
Neha Upadhyay ◽  
C.S. Ramaa

Background: Cancer being a complex disease, single targeting agents remain unsuccessful. This calls for “multiple targeting”, wherein a single drug is so designed that it will modulate the activity of multiple protein targets. Topoisomerase 2 (Top2) helps in removing DNA tangles and super-coiling during cellular replication, Casein Kinase 2 (CK2) is involved in the phosphorylation of a multitude of protein targets. Thus, in the present work, we have tried to develop dual inhibitors of Top2 and CK2. Objective: With this view, in the present work, 2 human proteins, Top2 and CK2 have been targeted to achieve the anti-proliferative effects. Methods: Novel 1-acetylamidoanthraquinone (3a-3y) derivatives were designed, synthesized and their structures were elucidated by analytical and spectral characterization techniques (FTIR, 1H NMR, 13C NMR and Mass Spectroscopy). The synthesized compounds were then subjected to evaluation of cytotoxic potential by the Sulforhodamine B (SRB) protein assay, using HL60 and K562 cell lines. Ten compounds were analyzed for Top2, CK2 enzyme inhibitory potential. Further, top three compounds were subjected to cell cycle analysis. Results: The compounds 3a to 3c, 3e, 3f, 3i to 3p, 3t and 3x showed excellent cytotoxic activity to HL-60 cell line indicating their high anti-proliferative potential in AML. The compounds 3a to 3c, 3e, 3f, 3i to 3p and 3y have shown good to moderate activity on K-562 cell line. Compounds 3e, 3f, 3i, 3x and 3y were found more cytotoxic than standard doxorubicin. In cell cycle analysis, the cells (79-85%) were found to arrest in the G0/G1 phase. Conclusion: We have successfully designed, synthesized, purified and structurally characterized 1- acetylamidoanthraquinone derivatives. Even though our compounds need design optimization to further increase enzyme inhibition, their overall anti-proliferative effects were found to be encouraging.


1987 ◽  
Vol 20 (2-3) ◽  
pp. 153-160 ◽  
Author(s):  
Christine L. Mummery ◽  
Marga A. van Rooijen ◽  
Stieneke E. van den Brink ◽  
Siegfried W. de Laat

2018 ◽  
Vol 61 (11) ◽  
pp. 837-846 ◽  
Author(s):  
Chandan Kumar ◽  
Rohit Sharma ◽  
Tapas Das ◽  
Aruna Korde ◽  
Haladhar Sarma ◽  
...  

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