Loading...
Small PARP inhibitor PJ-34 induces cell cycle arrest and apoptosis of adult T-cell leukemia cells
Bai, Xue Tao Moles, Ramona Chaib-Mezrag, Hassiba Nicot, Christophe
Bai, Xue Tao
Moles, Ramona
Chaib-Mezrag, Hassiba
Nicot, Christophe
Citations
Altmetric:
Abstract
Background
HTLV-I is associated with the development of an aggressive form of lymphocytic leukemia known as adult T-cell leukemia/lymphoma (ATLL). A major obstacle for effective treatment of ATLL resides in the genetic diversity of tumor cells and their ability to acquire resistance to chemotherapy regimens. As a result, most patients relapse and current therapeutic approaches still have limited long-term survival benefits. Hence, the development of novel approaches is greatly needed.
Methods
In this study, we found that a small molecule inhibitor of poly (ADP-ribose) polymerase (PARP), PJ-34, is very effective in activating S/G2M cell cycle checkpoints, resulting in permanent cell cycle arrest and reactivation of p53 transcription functions and caspase-3-dependent apoptosis of HTLV-I-transformed and patient-derived ATLL tumor cells. We also found that HTLV-I-transformed MT-2 cells are resistant to PJ-34 therapy associated with reduced cleaved caspase-3 activation and increased expression of RelA/p65.
Conclusion
Since PJ-34 has been tested in clinical trials for the treatment of solid tumors, our results suggest that some ATLL patients may be good candidates to benefit from PJ-34 therapy.
Description
A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author’s publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.
Date
2015-10-23
Journal Title
Journal ISSN
Volume Title
Publisher
BioMed Central
Research Projects
Organizational Units
Journal Issue
Keywords
Citation
Bai, Xue Tao, Ramona Moles, Hassiba Chaib-Mezrag, and Christophe Nicot. "Small PARP Inhibitor PJ-34 Induces Cell Cycle Arrest and Apoptosis of Adult T-cell Leukemia Cells." Journal of Hematology & Oncology (2015): n. pag. http://dx.doi.org/10.1186/s13045-015-0217-2