Tubulysin A is a highly cytotoxic peptide with antimitotic activity that induces depletion of cell microtubules and triggers the apoptotic process. Treated cells accumulated in the G(2)/M phase. Tubulysin A inhibited tubulin polymerization more efficiently than vinblastine and induced depolymerization of isolated microtubule preparations. Microtubule depolymerizotion could not be prevented by preincubation with epothilone B and paclitaxel, neither in cell-free systems nor in cell lines.

In addition to previously isolated ratjadone A we describe three new members of this family, ratjadones B, C, and D, from another strain of the myxobacterium Sorangium cellulosum. We have investigated the properties of these ratjadones with respect to their activity on mammalian cell lines. We found IC50 values in the picomolar range and a significant increase in the size of nuclei. A further examination showed that they inhibit the export of the leucine-rich nuclear export signal (LR-NES) containing proteins in different cell lines.

Disorazol A,, a macrocyclic polyketide compound that is produced by the myxobacterium Sorangium cellulosum showed a remarkably high cytostatic activity. It inhibited the proliferation of different cancer cell lines including a multi drug-resistant KB line at low picomolar levels. In presence of disorazol A I, the nuclei of the cells increased in size and the cells often became multinucleate. Low concentrations of disorazol (<100 muM) induced an apoptotic process, characterized by enhanced capase-3 activity and DNA laddering, and abnormal, multipolar mitotic spindles.