Nordihydroguaiaretic acid, of a new family of microtubule-stabilizing agents, shows effects differentiated from paclitaxel.
Nordihydroguaiaretic acid (NDGA) protected microtubules in NRK cells from depolymerization caused by structurally and functionally diverse drugs such as nocodazole, colchicine, vinblastine, and ilimaquinone. Hitherto reported drugs, although structurally unrelated to paclitaxel, stabilize microtubules in a way similar to that of paclitaxel and compete for paclitaxel binding to tubulin. However, NDGA had activity toward microtubules different from the effects of paclitaxel. In NRK cells, paclitaxel caused microtubule bundle formation in the presence and absence of microtubule-depolymerizing drugs. However, microtubule bundle did not form, and microtubules radiated from the microtubule-organizing center, in cells treated with NDGA. Acceleration of tubulin polymerization in vitro by paclitaxel was strong but that by NDGA was weak. Microtubules polymerized in vitro in the presence of paclitaxel, but not those polymerized in the presence of NDGA, resisted the effects of cold. NDGA seemed to bind to tubulin, but did not compete for [3H]paclitaxel binding to tubulin. These observations indicate that NDGA belongs to a novel family of microtubule-stabilizing drugs.
Nakamura
Machiko
M
Animal and Cellular Systems Laboratory, RIKEN, Institute of Physical and Chemical Research, Hirosawa 2-1, Wako-shi, Saitama 351-0198, Japan.
Nakazawa
Junko
J
Usui
Takeo
T
Osada
Hiroyuki
H
Kono
Yoshiki
Y
Takatsuki
Akira
A
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D007202:Indicators and Reagents; D009637:Masoprocol / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D017239:Paclitaxel / Q000494:pharmacology*; D011485:Protein Binding; D014404:Tubulin / Q000378:metabolism; D000520:alpha-Glucosidases / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D007202:Indicators and Reagents; D014404:Tubulin; D009637:Masoprocol; D000520:alpha-Glucosidases; D017239:Paclitaxel