Effects of (+)-, (-)- and (+/-)-indenestrols A and B on microtubule distribution and cytotoxicity in Chinese hamster V79 cells.
We have reported that (+)-, (-)- and (+/-)-indenestrols A and B (IA and IB respectively) inhibit the polymerization of microtubule proteins isolated from porcine brain in vitro. In this study, the effects of (+)-, (-)- and (+/-)-IA and IB on the relative plating efficiency, chromosome number and cellular microtubular architecture of Chinese hamster V79 cells, detected with a fluorescent anti-tubulin antibody, were investigated. The results indicated that the effect of (+/-)-IA was similar to that of diethylstilbestrol and that of (+/-)-IB was greater than that of (+/-)-IA. We also determined the effects of the optically active IA and IB isomers and found that the rank order of cytotoxic activity of the IA and IB series was: (-)-IA > (+/-)-IA > (+)-IA and (+/-)-IB > or = (-)-IB > (+)-IB. Furthermore, we studied the intracellular disturbance of microtubule formation induced by these compounds and found that (-)-IA had by far the greatest disruptive effect.
Oda
T
T
Division of Biochemistry, Kyoritsu College of Pharmacy, Tokyo, Japan.
Sakakibara
Y
Y
Ichinoseki
K
K
Aizu-Yokota
E
E
Sato
Y
Y
D000782:Aneuploidy; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005347:Fibroblasts / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D007192:Indenes / Q000633:toxicity*; D008870:Microtubules / Q000187:drug effects*; D014404:Tubulin / Q000096:biosynthesis* / Q000737:chemistry
D004968:Estrogens, Non-Steroidal; D007192:Indenes; D014404:Tubulin; C047437:indenestrol; C047501:indenestrol B