Dolastatin-10 induces polyploidy, telomeric associations and apoptosis in a murine melanoma cell line

Abstract

Our purpose was to study the effects of dolastatin-10 (Dol-10) on chromosome morphology, telomeric associations, induction of polyploidy and cell death in a metastatic murine melanoma cell line, K1735 clone X-21. Murine melanoma cells were treated with various concentrations (10 ng/ml, 100 ng/ml and 1000 ng/ml) of Dol-10 for 4, 24 and 72 h continuously and harvested immediately without recovery. In another set of experiments, cells were treated for 4 h with the same concentrations, washed with prewarmed medium and then allowed to recover in drug-free medium for 24 h and subsequently harvested. Our preliminary results indicated: i) a drug-mediated increase in the frequency of metaphases, with telomeric associations resulting in multicentric and ring configurations; ii) induction of clumping in metaphase chromosomes; iii) induction of polyploidy as a result of endoreduplication; iv) formation of micronucleated cells; and v) induction of cell death. These observations indicated that Dol-10 could be a potent antineoplastic drug against malignant melanoma. In addition to its reported interaction with cell microtubules, the mechanism of action of Dol-10 may be mediated through the loss of telomeric repeats and induction of chromosome aberrations.