Glycosylated podophyllotoxin congeners: loss of microtubule inhibition and permission of invasion in vitro.
Podophyllotoxin (PPT) and its glycosylated congeners, 4'-demethylepipodophyllotoxin 9-[4,6-O-(R)-ethylidene-beta-D-glucopyranoside] (VP-16-213) and 4'-demethylepipodophyllotoxin 9-[4,6-O-(R)-thenylidene-beta-D-glucopyranoside] (VM-26), were studied for their effects on the following activities of MO4 mouse fibrosarcoma cells in vitro: growth as an aggregate in culture on a gyrotory shaker, directional migration from an aggregate explanted on glass, organization of the cytoplasmic microtubule complex as inferred from immunostaining with an antiserum against tubulin, and invasion into fragments of 9-day-old embryonic chick cardiac muscle. At concentrations that inhibited growth (greater than or equal to 0.03 microgram/ml), PPT arrested directional migration, abolished the cytoplasmic microtubule complex, and interfered with invasion. VM-26 (0.1-1.0 microgram/ml) and VP-16-213 (1-30 micrograms/ml) interfered with growth but permitted directional migration, organization of the cytoplasmic microtubule complex, and invasion. These observations imply that microtubule inhibitors are anti-invasive because they interfere with the assembly of the cytoplasmic microtubule complex and not because they inhibit growth.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002642:Chick Embryo; D005047:Etoposide / Q000494:pharmacology*; D005354:Fibrosarcoma / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000187:drug effects*; D009206:Myocardium / Q000473:pathology; D009924:Organ Culture Techniques; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013713:Teniposide / Q000494:pharmacology*
D005047:Etoposide; D013713:Teniposide; D011034:Podophyllotoxin