Growth and ultrastructural responses of T-47D human breast tumor cells to treatment with mitoxantrone.

Mitoxantrone is a new anthracenedione derivative that suppresses cell proliferation in the T-47D human breast tumor cell line as revealed by colony-forming assay in soft agar and growth study in monolayer culture. One-hour drug exposure at 10(-9) M, 10(-7) M, and 10(-5) M reduced colony formation to 30%, 3%, and 0.5% of the control value, respectively. Little inhibition of cell growth was observed in monolayer cultures after 24 hr treatment with 10(-9) or 10(-8) M mitoxantrone, but a sharp decline occurred between 10(-6) M and 10(-5) M. Cytotoxicity was evident after 24 hr treatment with 10(-4) M drug; fewer than 10% of the cells survived. [3H]thymidine incorporation declined rapidly between 10(-9) M and 10(-6) M, revealing the potent inhibitory effect of mitoxantrone on DNA synthesis and cell proliferation. Ultrastructural examination revealed nucleolar alterations including dissociation and segregation of fibrillar and granular components, suggesting that this organelle is a principal intracellular target of mitoxantrone.