Resistance to thapsigargin-induced intracellular calcium mobilization in a multidrug resistant tumour cell line.
A multidrug resistant (MDR) cell line, derived from the human leukaemic cell K562 and selected for its resistance to Vincristine, was shown to be resistant to Thapsigargin (TG). A concentration of 50 nM TG was toxic to K562 cells whereas the MDR cell line, known as Lucena I cells, survived unaffected for up to seven days in culture. Similarly, no intracellular Ca2+ mobilization was observed in the MDR cell line treated with TG. This effect was not a result of TG extrusion by P glycoprotein (Pgp), as no mobilization was observed even in the presence of the Pgp inhibitors Verapamil (5 microM) and Cyclosporin A (0.16 microM). In the present study, both cell lines expressed comparable levels of Bcl-2 making it unlikely that Bcl-2 was involved in this process. Similarly, no overexpression of the endoplasmic reticulum Ca2+ ATPase (SERCA) could be detected in the MDR cell line and Ca2+ uptake by vesicles of the two cell types were equally sensitive to TG. These results confirm that MDR cells do not mobilize Ca2+ in the presence of TG but go against the possibility that this might be due to TG extrusion or to the overexpression of a resistant SERCA isoform.
Laboratório de Imunologia Tumoral, Departamento de Bioquímica Medica, Universidade Federal do Rio de Janeiro, Brazil.
Karen
K
Wagner-Souza
Juliana
J
Echevarria-Lima
Louise A P
LA
Rodrigues
Marcelo
M
Reis
Vivian M
VM
Rumjanek
D000970:Antineoplastic Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020014:K562 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019284:Thapsigargin / Q000494:pharmacology*
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D019284:Thapsigargin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium