Non-ionic detergent Tween 80 modulates VP-16 resistance in classical multidrug resistant K562 cells via enhancement of VP-16 influx.
The non-ionic detergent Tween 80, which is used as a solvent for lipophilic drugs such as VP-16 and Taxotere, was found to reverse VP-16 resistance of the P-glycoprotein-associated multidrug resistance phenotype via increasing VP-16 influx. In adriamycin-resistant human chronic myelogenous leukemia K562 cells (K562/ADM), which overexpress mdr1 mRNA, the accumulation of VP-16 was only about 10% that in wild-type K562 cells. Tween 80 enhanced VP-16 accumulation in K562/ADM cells but did not influence VP-16 accumulation in parental K562 cells. VP-16 efflux was rapid and similar in both sensitive and resistant cell lines and was not blocked by Tween 80 or verapamil. Under glucose-free conditions, VP-16 accumulation in K562/ADM cells was only half of that in K562 cells. Tween 80 increased VP-16 accumulation in K562/ADM cells in glucose-free medium. In growth inhibition assay, Tween 80 reversed K562/ADM sensitivity to VP-16 without cell damage. Taken together, Tween 80 reverses VP-16 sensitivity in multidrug-resistant K562 cells by increasing influx, which is considered to be the primary mechanism of VP-16 resistance in K562/ADM cells.
Yamazaki
T
T
The First Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. tyamaza@med.nihon-u.ac.jp
Sato
Y
Y
Hanai
M
M
Mochimaru
J
J
Tsujino
I
I
Sawada
U
U
Horie
T
T
D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D004347:Drug Interactions; D018432:Drug Resistance, Multiple; D005047:Etoposide / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D020014:K562 Cells / Q000187:drug effects* / Q000378:metabolism; D011136:Polysorbates / Q000494:pharmacology*; D013501:Surface-Active Agents / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D011136:Polysorbates; D013501:Surface-Active Agents; D005047:Etoposide