Golgi complex is brefeldin A resistant in multidrug resistant cells.
The multidrug resistance (MDR) is one of the main reasons for chemotherapeutic failures in cancer patients. The overexpression of mdr1 gene product, P-glycoprotein (Pgp), leads to the appearance of resistant tumor cells. In the previous paper (Erokhina, 1997) we have demonstrated that the first stages of Pgp-mediated MDR are accompanied by the reorganization of cytoskeleton elements and the vacuolar system. These data were true for two independently isolated sublines of Syrian hamster embryo fibroblasts transformed by Raus sarcoma virus. In this study, we continued the investigation of the properties of the vacuolar system in Pgp-expressing cells. Brefeldin A (BFA), which is not a Pgp substrate, affects different elements of the vacuolar system and blocks vesicular transport. Our data demonstrate that BFA has different effects on parental and resistant cells. In parental cells, the Golgi apparatus and vesicular transport are sensitive to BFA, while in resistant sublines, BFA affects the vesicular transport but not the Golgi apparatus structure. We discuss the existence of similar and different BFA targets in parental and resistant cells and their role in the evolution of multidrug resistance mechanisms.
Erokhina
M V
MV
Institute of Carcinogenesis, Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow. rak@sunny.aha.ru
Stavrovskaya
A A
AA
Onishchenko
G E
GE
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology*; D002461:Cell Line, Transformed; D006224:Cricetinae; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D018432:Drug Resistance, Multiple; D006056:Golgi Apparatus / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure*; D008647:Mesocricetus; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D011500:Protein Synthesis Inhibitors; D020126:Brefeldin A