The potential anticancer agent PK11195 induces apoptosis irrespective of p53 and ATM status in chronic lymphocytic leukemia cells

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 leu...

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Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2007
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/127632
Acceso en línea:https://hdl.handle.net/2445/127632
Access Level:acceso abierto
Palabra clave:Apoptosi
Leucèmia limfocítica crònica
Quimioteràpia
Apoptosis
Chronic lymphocytic leukemia
Chemotherapy
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spelling The potential anticancer agent PK11195 induces apoptosis irrespective of p53 and ATM status in chronic lymphocytic leukemia cellsSantidrián, Antonio F.Cosialls Castel, Ana MªColl Mulet, LlorençIglesias i Serret, DanielFrías Sanchez, Mercè deGonzález Gironés, Diana M.Campàs Moya, ClaraDomingo, AliciaPons i Irazazábal, GabrielGil i Santano, JoanApoptosiLeucèmia limfocítica crònicaQuimioteràpiaApoptosisChronic lymphocytic leukemiaChemotherapyBackground 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.European Hematology Association2019201920072019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion8 p.application/pdfhttps://hdl.handle.net/2445/127632Articles publicats en revistes (Ciències Fisiològiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3324/haematol.11194Hematology Journal, 2007, vol. 92, num. 12, p. 1631-1638https://doi.org/10.3324/haematol.11194(c) European Hematology Association, 2007info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1276322026-05-29T05:05:01Z
dc.title.none.fl_str_mv The potential anticancer agent PK11195 induces apoptosis irrespective of p53 and ATM status in chronic lymphocytic leukemia cells
title The potential anticancer agent PK11195 induces apoptosis irrespective of p53 and ATM status in chronic lymphocytic leukemia cells
spellingShingle The potential anticancer agent PK11195 induces apoptosis irrespective of p53 and ATM status in chronic lymphocytic leukemia cells
Santidrián, Antonio F.
Apoptosi
Leucèmia limfocítica crònica
Quimioteràpia
Apoptosis
Chronic lymphocytic leukemia
Chemotherapy
title_short The potential anticancer agent PK11195 induces apoptosis irrespective of p53 and ATM status in chronic lymphocytic leukemia cells
title_full The potential anticancer agent PK11195 induces apoptosis irrespective of p53 and ATM status in chronic lymphocytic leukemia cells
title_fullStr The potential anticancer agent PK11195 induces apoptosis irrespective of p53 and ATM status in chronic lymphocytic leukemia cells
title_full_unstemmed The potential anticancer agent PK11195 induces apoptosis irrespective of p53 and ATM status in chronic lymphocytic leukemia cells
title_sort The potential anticancer agent PK11195 induces apoptosis irrespective of p53 and ATM status in chronic lymphocytic leukemia cells
dc.creator.none.fl_str_mv 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
author Santidrián, Antonio F.
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Apoptosi
Leucèmia limfocítica crònica
Quimioteràpia
Apoptosis
Chronic lymphocytic leukemia
Chemotherapy
topic Apoptosi
Leucèmia limfocítica crònica
Quimioteràpia
Apoptosis
Chronic lymphocytic leukemia
Chemotherapy
description 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.
publishDate 2007
dc.date.none.fl_str_mv 2007
2019
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/127632
url https://hdl.handle.net/2445/127632
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3324/haematol.11194
Hematology Journal, 2007, vol. 92, num. 12, p. 1631-1638
https://doi.org/10.3324/haematol.11194
dc.rights.none.fl_str_mv (c) European Hematology Association, 2007
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) European Hematology Association, 2007
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 8 p.
application/pdf
dc.publisher.none.fl_str_mv European Hematology Association
publisher.none.fl_str_mv European Hematology Association
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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