Breast cancer (BCA) represents the highest incidence of death in 35- to 60-year-old women. Above all,
hormone unresponsive BCA is still associated with poorer prognosis than
hormone receptor expressing malign, mammary
tumors. There is a consistent need for effective compounds to treat especially the first variant of this disease. Therefore, we investigated the cytotoxic effects of the marine polyether
triterpenoid dehydrothyrsiferol (DT) in four BCA cell lines.
Annexin V labeling revealed higher rates of DT-induced apoptosis in
hormone insensitive than in
estrogen receptor expressing cells. Flow cytometric analysis of combined DNA fragmentation and total
DNA labeling allowed us to ascribe apoptotic cells to their cell cycle stage. Although, high cell mortality was detected in
mitogen dependent G(1)-phase, time, concentration, and cell line dependent populations of apoptotic cells were also found to be of S-phase and G(2)/M-phase origin. These results suggest that the induction of apoptosis by DT might be transduced through more than one effector pathway. Cell cycle distributions and
5-bromo-2'-deoxyuridine incorporation varied in a treatment dependent manner and differed from control experiments with
colchicine and
doxorubicin which exclude that DT functions as a mitosis inhibitor. In summary, we propose that DT might be an interesting candidate for an
antitumor drug development regimen.