Endonuclease Activation and Chromosomal DNA Fragmentation during Apoptosis in Leukemia Cells

2006 ◽  
Vol 84 (1) ◽  
pp. 31-37 ◽  
Author(s):  
Akira Yoshida ◽  
Yves Pommier ◽  
Takanori Ueda
2020 ◽  
Author(s):  
Ryo Okada ◽  
Sho Sugawara ◽  
Tze Mun Loo ◽  
Kenichi Miyata ◽  
Kaoru Kato ◽  
...  

2017 ◽  
Vol 45 (07) ◽  
pp. 1497-1511 ◽  
Author(s):  
Shinya Okubo ◽  
Takuhiro Uto ◽  
Aya Goto ◽  
Hiroyuki Tanaka ◽  
Tsuyoshi Nishioku ◽  
...  

Berberine (BBR), an isoquinoline alkaloid, is a well-known bioactive compound contained in medicinal plants used in traditional and folk medicines. In this study, we investigated the subcellular localization and the apoptotic mechanisms of BBR were elucidated. First, we confirmed the incorporation of BBR into the cell visually. BBR showed antiproliferative activity and promptly localized to the nucleus from 5[Formula: see text]min to 15[Formula: see text]min after BBR treatment in HL-60 human promyelocytic leukemia cells. Next, we examined the antiproliferative activity of BBR (1) and its biosynthetically related compounds (2-7) in HL-60 cells. BBR exerted strongest antiproliferative activity among 1-7 and the results of structures and activity relation suggested that a methylenedioxyl group in ring A, an [Formula: see text]-alkyl group at C-9 position, and the frame of isoquinoline may be necessary for antiproliferative activity. Moreover, BBR showed the most potent antiproliferative activity in HL-60 cells among human cancer and normal cell lines tested. Next, we examined the effect of BBR on molecular events known as apoptosis induction. In HL-60 cells, BBR induced chromatin condensation and DNA fragmentation, and triggered the activation of PARP, caspase-3 and caspase-8 without the activation of caspase-9. BBR-induced DNA fragmentation was abolished by pretreatment with inhibitors against caspase-3 and caspase-8, but not against caspase-9. ERK and p38 were promptly phosphorylated after 15 min of BBR treatment, and this was correlated with time of localization to the nucleus of BBR. These results demonstrated that BBR translocated into nucleus immediately after treatments and induced apoptotic cell death by activation of caspase-3 and caspase-8.


2016 ◽  
Vol 22 (5) ◽  
pp. 354-359 ◽  
Author(s):  
José-Manuel Rodríguez-Martínez ◽  
Rebeca Santiso ◽  
Jesús Machuca ◽  
Germán Bou ◽  
Álvaro Pascual ◽  
...  

Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1305-1309 ◽  
Author(s):  
CW Distelhorst

Abstract The present study was undertaken to investigate the potential role of glucocorticoid-induced DNA damage in the lysis of human lymphoid leukemia cells by glucocorticoids. Lymphoblasts were isolated from patients with acute lymphoblastic leukemia (ALL) or chronic myelogenous leukemia (CML) in blast crisis and cultured in vitro with or without dexamethasone. DNA was then purified from the cells and analyzed by agarose gel electrophoresis. Only high molecular weight (mol wt) DNA was present in cells cultured without dexamethasone, but a ladder of DNA fragments ranging in size from 180 to 200 base pairs (bp) to greater than 1,500 bp was present in cells cultured with dexamethasone. The DNA fragments were multiples of 180 to 200 bp, suggesting an internucleosomal site of DNA cleavage. The same pattern of DNA fragmentation was detected in normal thymocytes isolated from adrenalectomized rats following in vivo treatment with dexamethasone and in S49 mouse thymoma cells after in vitro incubation with dexamethasone. Dexamethasone-induced DNA fragmentation preceded overt loss of viability in glucocorticoid-sensitive cells but was not detected in two variants of the S49 cell line that are glucocorticoid resistant owing to glucocorticoid receptor defects. The results suggest that glucocorticoids kill human lymphoblastic leukemia cells and both normal and malignant murine thymocytes by a common mechanism that involves glucocorticoid induction of an endonucleolytic activity with cleavage of genomic DNA.


2012 ◽  
Vol 194 (12) ◽  
pp. 967-975 ◽  
Author(s):  
María Tamayo ◽  
Rebeca Santiso ◽  
Jaime Gosálvez ◽  
Germán Bou ◽  
María del Cármen Fernández ◽  
...  

1997 ◽  
Vol 117 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Akihiro Kataoka ◽  
Masaru Kubota ◽  
Ikuya Usami ◽  
Akiro Okuda ◽  
Ying Wei Lin ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Abdullahi Shafiu Kamba ◽  
Maznah Ismail ◽  
Tengku Azmi Tengku Ibrahim ◽  
Zuki Abu Bakar Zakaria ◽  
Lawal Hassan Gusau

Bones are the most frequent site for breast cancer cells to settle and spread (metastasise); bone metastasis is considered to have a substantial impact on the quality of patients with common cancers. However, majority of breast cancers develop insensitivity to conventional chemotherapy which provides only palliation and can induce systemic side effects. In this study we evaluated the effect of free Dox and CaCO3/Dox nanocrystal on MCF-7 breast cancer using MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide), neural red, and lactate dehydrogenase colorimetric assays while DNA fragmentation and BrdU genotoxicity were also examined. Apoptogenic protein Bax, cytochrome C, and caspase-3 protein were analysed. Morphological changes of MCF-7 were determined using contrast light microscope and scanning and transmission electron microscope (SEM and TEM). The findings of the analysis revealed higher toxicity of CaCO3/Dox nanocrystal and effective cells killing compared to free Dox, morphological changes such as formation of apoptotic bodies, membrane blebbing, and absent of microvilli as indicated by the SEM analysis while TEM revealed the presence of chromatin condensation, chromosomal DNA fragmentation, cell shrinkage, and nuclear fragmentation. Results of TUNEL assay verified that most of the cells undergoes apoptosis by internucleosomal fragmentation of genomic DNA whereas the extent of apoptotic cells was calculated using the apoptotic index (AI). Therefore, the biobased calcium carbonate nanocrystals such as Dox carriers may serve as an alternative to conventional delivery system.


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