Disruption of microfilaments by cytochalasin B decreases accumulation of cisplatin in human epidermal carcinoma and liver carcinoma cell lines.
BACKGROUND
Although cisplatin is a frequently used cancer chemotherapeutic drug, its effectiveness is hindered by the development of resistance in cancer cells. In order to understand the reason(s) for this resistance, the mechanism of uptake of cisplatin into cells must be characterized. While several previous studies showed structural differences between cisplatin-sensitive and resistant cells, the influence of microfilaments, known to affect transport of molecules into cells, and the influence of certain biophysical characteristics of the plasma membrane needed clarification.


RESULTS
We show that resistant human epidermal carcinoma (KB-CP20) and liver carcinoma (BEL-7404-CP20) cells become relatively more resistant if their already weak microfilaments are degraded by cytochalasin B treatment (.5-2 microM). The sensitive counterparts of these cells with intact microfilaments are not significantly affected by this treatment. We also show that the "fluidity" of the plasma membrane and the membrane potential of the sensitive and resistant cells studied do not appear to influence the uptake of cisplatin into the cells.


CONCLUSIONS
Our results suggest that the status of the microfilament system influences the mechanism of uptake of cisplatin into cells.
Liang
Xing-Jie
XJ
Laboratory of Cell Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Yin
Jun-Jie
JJ
Taylor
Barbara
B
Winkovitch
Stephen M
SM
Garfield
Susan H
SH
Shen
Ding-Wu
DW
Gottesman
Michael M
MM
Aszalos
Adorjan
A
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D001692:Biological Transport / Q000187:drug effects; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D002945:Cisplatin / Q000378:metabolism* / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D007624:KB Cells / Q000187:drug effects / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008560:Membrane Fluidity / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*
D003571:Cytochalasin B; D002945:Cisplatin