Inhibition of GST-pi nuclear transfer increases mantle cell lymphoma sensitivity to cisplatin, cytarabine, gemcitabine, bortezomib and doxorubicin

Anticancer Res. 2010 Oct;30(10):3951-7.

Abstract

Purpose: Mantle cell lymphoma (MCL) is a chemoresistant lymphoma overexpressing the class pi glutathione-S-transferase (GST-pi). The nuclear localisation of GST-pi is induced by chemotherapy and is correlated to cell resistance. In this study, the effect of the Agaricus bisporus lectin (ABL), a GST-pi nuclear transfer inhibitor, on the chemosensitivity of MCL cells was investigated.

Methods: The proliferation of three MCL cell lines was evaluated in the presence of doxorubicin (DOX), cisplatin (CDDP), cytarabine (Ara-C), gemcitabine (GEM) or bortezomib with or without ABL pre-treatment.

Results: The cytotoxic activities of CDDP, Ara-C, GEM and bortezomib were increased in all cell lines. The DOX cytotoxic activity was enhanced in two of three cell lines. The inhibition of GST-pi nuclear transfer led to the potentialisation of all drug combinations.

Conclusion: The inhibition of the nuclear transfer of GST-pi increases the MCL sensitivity to DOX, CDDP, Ara-C, GEM and bortezomib, alone or in combination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Boronic Acids / administration & dosage
  • Boronic Acids / pharmacology
  • Bortezomib
  • Cell Growth Processes / drug effects
  • Cell Line, Tumor
  • Cisplatin / administration & dosage
  • Cisplatin / pharmacology
  • Cytarabine / administration & dosage
  • Cytarabine / pharmacology
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Doxorubicin / administration & dosage
  • Doxorubicin / pharmacology
  • Drug Screening Assays, Antitumor
  • Gemcitabine
  • Glutathione S-Transferase pi / antagonists & inhibitors*
  • Glutathione S-Transferase pi / metabolism
  • Humans
  • Lectins / administration & dosage
  • Lectins / pharmacology
  • Lymphoma, Mantle-Cell / drug therapy*
  • Lymphoma, Mantle-Cell / enzymology*
  • Lymphoma, Mantle-Cell / pathology
  • Pyrazines / administration & dosage
  • Pyrazines / pharmacology

Substances

  • Agaricus lectins
  • Antineoplastic Agents
  • Boronic Acids
  • Lectins
  • Pyrazines
  • Cytarabine
  • Deoxycytidine
  • Bortezomib
  • Doxorubicin
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Cisplatin
  • Gemcitabine