scholarly journals Antiproliferative activity of goniothalamin enantiomers involves DNA damage, cell cycle arrest and apoptosis induction in MCF-7 and HB4a cells

2015 ◽  
Vol 30 (1) ◽  
pp. 250-263 ◽  
Author(s):  
Simone Cristine Semprebon ◽  
Lilian Areal Marques ◽  
Gláucia Fernanda Rocha D'Epiro ◽  
Elaine Aparecida de Camargo ◽  
Glenda Nicioli da Silva ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Antiproliferative Activity ◽  
Apoptosis Induction ◽  
Damage Cell ◽  
Cycle Arrest ◽  
Mcf 7

scholarly journals Effective Cellular Transport of Ortho-Halogenated Sulfonamide Derivatives of Metformin Is Related to Improved Antiproliferative Activity and Apoptosis Induction in MCF-7 Cells

2020 ◽  
Vol 21 (7) ◽  
pp. 2389 ◽  
Author(s):  
Magdalena Markowicz-Piasecka ◽  
Ibrahim Komeil ◽  
Johanna Huttunen ◽  
Joanna Sikora ◽  
Kristiina M. Huttunen
Keyword(s):  
Cell Cycle ◽  
Chemical Modification ◽  
Cell Cycle Arrest ◽  
Cellular Uptake ◽  
Antiproliferative Activity ◽  
Breast Cancer Cell Lines ◽  
Cellular Transport ◽  
Apoptosis Induction ◽  
Cycle Arrest ◽  
Mcf 7

Metformin is a substrate for plasma membrane monoamine transporters (PMAT) and organic cation transporters (OCTs); therefore, the expression of these transporters and interactions between them may affect the uptake of metformin into tumor cells and its anticancer efficacy. The aim of this study was to evaluate how chemical modification of metformin scaffold into benzene sulfonamides with halogen substituents (compounds 1–9) may affect affinity towards OCTs, cellular uptake in two breast cancer cell lines (MCF-7 and MDA-MB-231) and antiproliferative efficacy of metformin. The uptake of most sulfonamides was more efficient in MCF-7 cells than in MDA-MB-231 cells. The presence of a chlorine atom in the aromatic ring contributed to the highest uptake in MCF-7 cells. For instance, the uptake of compound 1 with o-chloro substituent in MCF-7 cells was 1.79 ± 0.79 nmol/min/mg protein, while in MDA-MB-231 cells, the uptake was considerably lower (0.005 ± 0.0005 nmol/min/mg protein). The elevated uptake of tested compounds in MCF-7 was accompanied by high antiproliferative activity, with compound 1 being the most active (IC50 = 12.6 ± 1.2 µmol/L). Further studies showed that inhibition of MCF-7 growth is associated with the induction of early and late apoptosis and cell cycle arrest at the G0/G1 phase. In summary, the chemical modification of the biguanide backbone into halogenated sulfonamides leads to improved transporter-mediated cellular uptake in MCF-7 and contributes to the greater antiproliferative potency of studied compounds through apoptosis induction and cell cycle arrest.

Cr(VI) Induces DNA Damage, Cell Cycle Arrest and Polyploidization: A Flow Cytometric and Comet Assay Study inPisum sativum

2011 ◽  
Vol 24 (7) ◽  
pp. 1040-1047 ◽  
Author(s):  
Eleazar Rodriguez ◽  
Raquel Azevedo ◽  
Pedro Fernandes ◽  
Conceic¸ão Santos
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Comet Assay ◽  
Cell Cycle Arrest ◽  
Damage Cell ◽  
Cycle Arrest ◽  
Flow Cytometric

Celastrol Induced DNA Damage, Cell Cycle Arrest, and Apoptosis in Human Rheumatoid Fibroblast-Like Synovial Cells

2013 ◽  
Vol 41 (03) ◽  
pp. 615-628 ◽  
Author(s):  
Zengtao Xu ◽  
Guosheng Wu ◽  
Xu Wei ◽  
Xiuping Chen ◽  
Yitao Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Inflammatory Diseases ◽  
Annexin V ◽  
Synovial Fibroblasts ◽  
Damage Cell ◽  
Cycle Arrest ◽  
M Phase

Celastrol is one of the principal active ingredients of Tripterygium wilfordii Hook.f., a toxic Chinese medical herb traditionally prescribed for controlling pain and inhibiting inflammation in various chronic inflammatory diseases, including rheumatoid arthritis (RA). Resistance to apoptosis of fibroblast-like synoviocytes is considered a major characteristic of RA. In this study, we test celastrol's cytotoxic effect and potential mechanisms in human rheumatoid synovial fibroblasts (RA-FLS). In the cytotoxic assay, we found that celastrol dose-dependently decreased RA-FLS viability and increased LDH release. The apoptotic nuclear morphology was observed after celastrol treatment as determined by DAPI fluorescence staining. Flow cytometry analysis with PI and Annexin V revealed that celastrol induced RA-FLS cell cycle arrest in the G2/M phase and apoptosis. Furthermore, celastrol dramatically increased expression of Bax/Bcl-2, proteolytic cleavage of Caspase-3, -9, PARP, and decreased expression of FasR. In addition, celastrol treatment resulted in DNA damage. Collectively, we concluded that celastrol inhibits RA-FLS proliferation by inducing DNA damage, cell cycle arrest, and apoptosis in vitro, which might provide data for its application in RA treatment.

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