Glycosylated Podophyllotoxin Congeners: Loss of Microtubule Inhibition and Permission of Invasion In Vitro

• Published in: JNCI : Journal of the National Cancer Institute 1982-12, Vol.69 (6), p.1367-1374
• Main Authors: Mareel, Marc M., Dragonetti, Christian H., De Bruyne, Georges K., Van Cauwenberge, Rita M.-L.
• Format: Article
• Language: English
• Subjects: Animals; Cell Division - drug effects; Chick Embryo; Etoposide - pharmacology; Fibrosarcoma - metabolism; Mice; Microtubules - drug effects; Myocardium - pathology; Organ Culture Techniques; Podophyllotoxin - analogs & derivatives; Podophyllotoxin - pharmacology; Teniposide - pharmacology
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/69.6.1367

Podophyllotoxin (PPT) and its glycosylated congeners, 4-demethylepipodophyllotoxin 9-[4,6-O-(R)-ethylidene-{β-d-glucopyranoside] (VP-16-213) and 4′-demethylepipodophyllotoxin 9-[4,6-O-(R)-thenylidene-{β-d-glucopyranoside] (VM-26), were studied for their effects on the following activities of MO. 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 againsttubulin, and invasion into fragments of 9-day-old embryonic chick cardiac muscle. At concentrations that inhibited growth (≥0.03 μg/ml), PPT arrested directional migration, abolished the cytoplasmic microtubule complex, and interfered with invasion. VM-26 (0.1–1.0 μ/ml) and VP-16-213 (1–30 μ/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.