1. Institute of Biochemistry and Biophysics, University of Tehran 2. Institute of Biochemistry and Biophysics, University of Tehran
Abstract
Introduction
Mitoxantrone (novantrone®; dihydroxyanthracenedione) is a synthetically designed antineoplastic agent and structurally similar to classical anthracyclines. it is widely used as a potent chemotherapeutic component against various kinds of cancer. in the present study, cytotoxicity of mitoxantrone on non-adherent bone marrow cells was examined.
Methods
Hematopoietic stem cells were prepared and exposed to various concentrations of mitoxantrone (0-45μm) for 12h at 37°c under 5% co2 and fully humidified condition and viability determined by trypan blue exclusion and mtt assays. for morphological study, the cells were stained with ethidium bromide/ acridine orange and examined with fluorescence microscope.
Results
The results showed that mitoxantrone exhibited dose dependent cytotoxicity on the cells and upon increasing mitoxantrone concentration, viability of cells was decreased from 96% in the control to 52% in 2μm (ic50) of mitoxantrone. microscopic observation of stained cells showed that by increasing drug concentration, apoptosis/necrosis occurs in the cells by converting the green color of the control cells into orange/ red color of necrotic cells.
Conclusion
from the results it is concluded that mitoxantrone as a drug that is widely used in cancer chemotherapy is toxic for hematopoietic stem cells of bone marrow and preceed them into apoptosis/necrosis, suggestion that its usage in therapy must be down with caution.
Keywords
Mitoxantrone, anticancer drug, hematopoietic stem cells , side effect
