scholarly journals Small PARP inhibitor PJ-34 induces cell cycle arrest and apoptosis of adult T-cell leukemia cells

2015 ◽  
Vol 8 (1) ◽  
Author(s):  
Xue Tao Bai ◽  
Ramona Moles ◽  
Hassiba Chaib-Mezrag ◽  
Christophe Nicot
2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Christophe Nicot

Tumor suppressor functions are essential to control cellular proliferation, to activate the apoptosis or senescence pathway to eliminate unwanted cells, to link DNA damage signals to cell cycle arrest checkpoints, to activate appropriate DNA repair pathways, and to prevent the loss of adhesion to inhibit initiation of metastases. Therefore, tumor suppressor genes are indispensable to maintaining genetic and genomic integrity. Consequently, inactivation of tumor suppressors by somatic mutations or epigenetic mechanisms is frequently associated with tumor initiation and development. In contrast, reactivation of tumor suppressor functions can effectively reverse the transformed phenotype and lead to cell cycle arrest or death of cancerous cells and be used as a therapeutic strategy. Adult T-cell leukemia/lymphoma (ATLL) is an aggressive lymphoproliferative disease associated with infection of CD4 T cells by the Human T-cell Leukemia Virus Type 1 (HTLV-I). HTLV-I-associated T-cell transformation is the result of a multistep oncogenic process in which the virus initially induces chronic T-cell proliferation and alters cellular pathways resulting in the accumulation of genetic defects and the deregulated growth of virally infected cells. This review will focus on the current knowledge of the genetic and epigenetic mechanisms regulating the inactivation of tumor suppressors in the pathogenesis of HTLV-I.


2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Gaomei Chang ◽  
Wenqin Xiao ◽  
Zhijian Xu ◽  
Dandan Yu ◽  
Bo Li ◽  
...  

Pterostilbene is a natural 3,5-dimethoxy analog oftrans-resveratrol that has been reported to have antitumor, antioxidant, and anti-inflammatory effects. T-cell leukemia/lymphoma is one of the more aggressive yet uncommon non-Hodgkin lymphomas. Although there has been increasing research into T-cell leukemia/lymphoma, the molecular mechanisms of the antitumor effects of pterostilbene against this malignancy are still largely unknown. The aim of this study is to confirm the effects of pterostilbene in T-cell leukemia/lymphoma. Jurkat and Hut-78 cells treated with pterostilbene were evaluated for cell proliferation using Cell Counting Kit-8, and apoptosis, cell cycle progression, reactive oxygen species generation, and mitochondrial membrane potential were analyzed using flow cytometry. The level of protein expression was detected by western blot. The results demonstrated that pterostilbene significantly inhibited the growth of T-cell leukemia/lymphoma cell lines in vitro and induced apoptosis in a dose- and time-dependent manner. Moreover, pterostilbene treatment markedly induced S-phase cell cycle arrest, which was accompanied by downregulation of cdc25A, cyclin A2, and CDK2. Pterostilbene also induced the generation of reactive oxygen species and the loss of mitochondrial membrane potential and inhibited ERK1/2 phosphorylation. Taken together, our study demonstrated the potential of pterostilbene to be an effective treatment for T-cell leukemia/lymphoma.


2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Dominik Klumpp ◽  
Milan Misovic ◽  
Kalina Szteyn ◽  
Ekaterina Shumilina ◽  
Justine Rudner ◽  
...  

Messenger RNA data of lymphohematopoietic cancer lines suggest a correlation between expression of the cation channel TRPM2 and the antiapoptotic protein Bcl-2. The latter is overexpressed in various tumor entities and mediates therapy resistance. Here, we analyzed the crosstalk between Bcl-2 and TRPM2 channels in T cell leukemia cells during oxidative stress as conferred by ionizing radiation (IR). To this end, the effects of TRPM2 inhibition or knock-down on plasma membrane currents, Ca2+signaling, mitochondrial superoxide anion formation, and cell cycle progression were compared between irradiated (0–10 Gy) Bcl-2-overexpressing and empty vector-transfected Jurkat cells. As a result, IR stimulated a TRPM2-mediated Ca2+-entry, which was higher in Bcl-2-overexpressing than in control cells and which contributed to IR-induced G2/M cell cycle arrest. TRPM2 inhibition induced a release from G2/M arrest resulting in cell death. Collectively, this data suggests a pivotal function of TRPM2 in the DNA damage response of T cell leukemia cells. Apoptosis-resistant Bcl-2-overexpressing cells even can afford higher TRPM2 activity without risking a hazardous Ca2+-overload-induced mitochondrial superoxide anion formation.


2009 ◽  
Vol 52 (3) ◽  
pp. 191-192 ◽  
Author(s):  
N. Mori ◽  
F. Shirakawa ◽  
S. Murakami ◽  
S. Oda ◽  
S. Eto

Retrovirology ◽  
2011 ◽  
Vol 8 (1) ◽  
pp. 19 ◽  
Author(s):  
Keita Hagiya ◽  
Jun-ichirou Yasunaga ◽  
Yorifumi Satou ◽  
Koichi Ohshima ◽  
Masao Matsuoka

1994 ◽  
Vol 18 (2) ◽  
pp. 79-84 ◽  
Author(s):  
Shimeru Kamihira ◽  
Sunao Atogami ◽  
Hisashi Sohda ◽  
Saburo Momita ◽  
Kazuhiro Toryia ◽  
...  

1997 ◽  
Vol 21 (3) ◽  
pp. 211-216 ◽  
Author(s):  
Kakushi Matsushita ◽  
Naomichi Arima ◽  
Hideo Ohtsubo ◽  
Hiroshi Fujiwara ◽  
Shiroh Hidaka ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document