Vanadate is toxic to adherent- growing multidrug-resistant cells.
The development of multidrug resistance (MDR) is the primary cause of failure of cancer chemotherapy and circumventing this problem is a major challenge in oncology. Vanadate is known to inhibit the ATPase activity of the P-glycoprotein and multidrug-resistant associated protein. In the present study we show that adherent MDR cells are more sensitive to vanadate than adherent non-MDR ones, but the same is not true for suspension-growing cells. Vanadate induced stress fiber in the non-MDR adherent MDCK cell line, but destroyed the actin fibers of MDCK/60 and MA104 cells, two adherent MDR cell lines, suggesting that the sensitivity of these cells to vanadate is related to their actin cytoskeleton. The results suggest that vanadate may be used as an adjuvant in the chemotherapy of solid tumors, not only as an ATPase inhibitor but also because of its effect in the MDR cell cytoskeleton.
Capella
L S
LS
Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. mcapella@biof.ufrj.br
Alcantara
J S
JS
Moura-Neto
V
V
Lopes
A G
AG
Capella
M A
MA
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism; D004285:Dogs; D018432:Drug Resistance, Multiple; D006801:Humans; D020014:K562 Cells; D008253:Macaca mulatta; D018613:Microscopy, Confocal; D014638:Vanadates / Q000633:toxicity*
D018435:ATP Binding Cassette Transporter, Subfamily B; D000199:Actins; D014638:Vanadates; D000251:Adenosine Triphosphatases