The cytoskeleton as a subcellular target of the antineoplastic drug lonidamine
Malorni, W.; Meschini, S.; Matarrese, P.; Arancia, G.
Anticancer Research 12(6b): 2037-2045
1992
ISSN/ISBN: 0250-7005 PMID: 1295447 Document Number: 391244
Lonidamine (LND), a dichlorinated derivative of indazole-3-carboxylic acid, has proved to exert a powerful antiproliferative effect and to impair the energy metabolism of normal and neoplastic cells. A target effect of the drug on the cell membrane structure was hypothesized. Thus, in order to elucidate better the mechanism of action of LND, the drug effects on the cell surface as well as on main cytoskeletal elements, i.e. actin microfilaments, microtubules and intermediate filaments, were investigated. In particular, an immunocytochemical and ultrastructural study was performed using two different cell lines: epithelial squamous carcinoma (A431) and melanoma (M14)cells. Treatment with 0.89 mM LND for 8 hr induced a remarkable rearrangement of the F-actin molecules with the disaapperance of the stress fibers. As far as microtubules are concerned, formation of perinuclear patches of tubulin were detected after LND treatment. Intermediate filaments appeared to be differently affected by LN in the two cells types. Such changes were detected as an early phenomenon and the extent of the effects observed was positively related to the cell surface alterations and to the loss of cell viability, suggesting that the cytoskeletal elements might represent an additional target in the mechanisms of cytotoxic action of LND.