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In this study the ability of five novel anti-oestrogens [4-iodotamoxifen, pyrrolidino-4-iodotamoxifen, ethyl bromide tamoxifen (EBTx), ICI 164,384 (ICI 164) and ICI 182,780] to alter drug toxicity to multidrug resistant cell lines have been compared. The effect of these compounds on ATP-dependent vinblastine (VBL) transport was also tested using inside-out vesicles (IOV) prepared from highly P-glycoprotein (Pgp)-expressing CCRF-CEM/VBL1000 cells. The pure anti-oestrogen ICI 164 was most effective, enhancing doxorubicin and VBL toxicity to MCF-7Adr cells 25- and 35-fold, respectively, and was also the best inhibitor of ATP-dependent [3H]VBL accumulation by IOV. Pure anti-oestrogens, tamoxifen and iodotamoxifens completely reversed VBL resistance in the mdr1 transfected lung cancer cell line, S1/1.1, where resistance relative to wild-type cells was mediated solely by Pgp. The membrane impermeant tamoxifen derivative EBTx did not modify drug resistance, yet was as effective an inhibitor of VBL accumulation by inside-out Pgp-positive vesicles as tamoxifen. This indicates an intracellular role for tamoxifen and its derivatives in the modulation of Pgp-mediated drug resistance.
J Kirk, and
S K Syed, and
A L Harris, and
M Jarman, and
B D Roufogalis, and
I J Stratford, and
J Carmichael
February 1999,
Bioorganic & medicinal chemistry letters,
J Kirk, and
S K Syed, and
A L Harris, and
M Jarman, and
B D Roufogalis, and
I J Stratford, and
J Carmichael
January 2015,
Journal of Asian natural products research,
J Kirk, and
S K Syed, and
A L Harris, and
M Jarman, and
B D Roufogalis, and
I J Stratford, and
J Carmichael
October 1998,
British journal of cancer,
J Kirk, and
S K Syed, and
A L Harris, and
M Jarman, and
B D Roufogalis, and
I J Stratford, and
J Carmichael
June 2007,
Journal of natural products,
J Kirk, and
S K Syed, and
A L Harris, and
M Jarman, and
B D Roufogalis, and
I J Stratford, and
J Carmichael
January 2001,
Anti-cancer drug design,
J Kirk, and
S K Syed, and
A L Harris, and
M Jarman, and
B D Roufogalis, and
I J Stratford, and
J Carmichael
January 2019,
Frontiers in chemistry,
J Kirk, and
S K Syed, and
A L Harris, and
M Jarman, and
B D Roufogalis, and
I J Stratford, and
J Carmichael
June 1996,
European journal of cancer (Oxford, England : 1990),
J Kirk, and
S K Syed, and
A L Harris, and
M Jarman, and
B D Roufogalis, and
I J Stratford, and
J Carmichael
January 2003,
Biochemical pharmacology,
J Kirk, and
S K Syed, and
A L Harris, and
M Jarman, and
B D Roufogalis, and
I J Stratford, and
J Carmichael
January 2013,
Chemical & pharmaceutical bulletin,
J Kirk, and
S K Syed, and
A L Harris, and
M Jarman, and
B D Roufogalis, and
I J Stratford, and
J Carmichael
June 2008,
Biological & pharmaceutical bulletin,
