Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/127632
Title: | The potential anticancer agent PK11195 induces apoptosis irrespective of p53 and ATM status in chronic lymphocytic leukemia cells |
Author: | Santidrián, Antonio F. Cosialls Castel, Ana Mª Coll Mulet, Llorenç Iglesias i Serret, Daniel Frías Sanchez, Mercè de González Gironés, Diana M. Campàs Moya, Clara Domingo, Alicia Pons i Irazazábal, Gabriel Gil i Santano, Joan |
Keywords: | Apoptosi Leucèmia limfocítica crònica Quimioteràpia Apoptosis Chronic lymphocytic leukemia Chemotherapy |
Issue Date: | Dec-2007 |
Publisher: | European Hematology Association |
Abstract: | Background and Objectives The potential anticancer agent 1-(2-chlorophenyl-N-methylpropyl)-3-isoquinolinecarboxamide (PK11195), a translocator protein (18KDa) (TSPO) ligand, facilitates the induction of cell death by a variety of cytotoxic and chemotherapeutic agents. Primary chronic lymphocytic leukemia (CLL) cells overexpress TSPO. The aim of this study was to examine the effects of PK11195 on CLL cells. Design and Methods Using cytometric analysis, we studied the cytotoxic effects of PK11195 on peripheral B and T lymphocytes from patients with CLL and from healthy donors. Western blot and cytometric analyses were used to study the mitochondrial effects of PK11195 on CLL cells. Moreover, we analyzed the cytotoxic effect of PK11195 in patients' cells with mutated p53 or ATM. Results PK11195 induces apoptosis and had additive effects with chemotherapeutic drugs in primary CLL cells. Other TSPO ligands such as RO 5-4864 and FGIN-1-27 also induce apoptosis in CLL cells. PK11195 induces mitochondrial depolarization and cytochrome c release upstream of caspase activation, and dithiocyana-tostilbene-2,2-disulfonic acid (DIDS), a voltage-dependent anion channel (VDAC) inhibitor, inhibits PK11195-induced apoptosis, demonstrating a direct involvement of mitochondria. CLL cells and normal B cells are more sensitive than T cells to PK11195-induced apoptosis. Interestingly, PK11195 induced apoptosis in CLL cells irrespective of their p53 or ATM status. Interpretation and Conclusions These results suggest that PK11195 alone or in combination with chemotherapeutic drugs might be a new therapeutic option for the treatment of CLL. |
Note: | Reproducció del document publicat a: https://doi.org/10.3324/haematol.11194 |
It is part of: | Hematology Journal, 2007, vol. 92, num. 12, p. 1631-1638 |
URI: | http://hdl.handle.net/2445/127632 |
Related resource: | https://doi.org/10.3324/haematol.11194 |
ISSN: | 1466-4860 |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
565250.pdf | 221.4 kB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.