8-Cl-adenosine mediated cytotoxicity and sensitization of T-lymphoblastic leukemia cells to TNF alpha-induced apoptosis is via inactivation of NF-kappa B

These data show that 8-Cl-cAMP is cytotoxic to the lymphoblastic leukemia c ell line CEM and its vinblastine selected multidrug resistant derivative, C EM/VLB100 although PKA was not involved in these effects. The cytotoxic eff ects of 8-Cl-cAMP was abrogated by cotreatment with either ADA or IBMX whic h indicated a degradation form of s-CI-cAMP was needed for this cytotoxicit y. CEM and CEM/VLB100 cells displayed a notable sensitivity to 8-Cl-adenosi ne-induced growth inhibition and apoptosis. 8-Cl-adenosine increased the cy tosolic levels of I kappaB alpha which prevented NF-kappaB nuclear transloc ation. 8-Cl-adenosine also prevented TNF alpha -induced IkB decay and NF-ka ppaB activation in CEM and CEM/VLB100 cells. (C) 2001 Elsevier Science Ltd. All rights reserved.