Induction of differentiation and tetraploidy by long-term treatment of C6 rat glioma cells with erucylphosphocholine

Induction of differentiation represents a promising concept for chemotherap y of malignant gliomas, which are often refractory even to the combined tre atment with surgery, irradiation and chemotherapy. Since anti-neoplastic al kyl-phosphocholines can induce differentiation of leukemic cell lines, the effects of the intravenously applicable alkyl-phosphocholine-derivative eru cylphosphocholine (ErPC) on proliferation, morphology and differentiation o f the rat glioma cell line C6 was examined in vitro. Short-term exposure to ErPC induced accumulation of the cells in the G2/M-phase of the cell cycle and apoptotic cell death. In contrast, continuous exposure of C6 rat gliom a cells to sublethal ErPC doses (30 and 50 muM) caused both the formation o f a slower growing tetraploid cell population and astrocytic differentiatio n. No resistance to in vivo obtainable ErPC concentrations was observed dur ing this treatment. We conclude that ErPC-induced differentiation might be beneficial for a long-term adjuvant chemotherapy of low grade glioma.