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Selective Decrease of the Viability and the Sterol Content of Proliferating versus Quiescent Glioma Cells Exposed to 25-Hydroxycholesterol¹

Departments of Pediatrics, Neurology, and Biological Chemistry, Washington University School of Medicine, St. Louis, Missouri 63178

The effects of 25-hydroxycholesterol (25-OHC), a potent inhibitor of sterol synthesis, on the growth, viability, and sterol content of C-6 rat glioma cells have been studied. Suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and sterol synthesis in cells that were proliferating in medium supplemented with lipoprotein-poor fetal calf serum caused an arrest of growth after 24 hr. Prolonged incubation of serum-supplemented cells with 25-OHC resulted in a loss of morphological integrity and an 80% decline in cell viability, determined by trypan blue dye exclusion. In contrast, C-6 cells that were induced to enter a quiescent state by removal of serum from the medium remained viable and morphologically differentiated in the presence of 25-OHC. Following the addition of whole fetal calf serum to the medium, serum-free cells that had been incubated with 25-OHC for 3 days were able to resume proliferation. The selective killing of proliferating C-6 glioma cells by 25-OHC was correlated with a 45 to 50% decline in the sterol/phospholipid molar ratio, whereas the sterol/phospholipid ratio in the quiescent cells was not affected by 25-OHC. The results suggest that inhibitors of sterol synthesis may have potential as agents that might selectively decrease the growth and viability of glioma cells in the central nervous system without detriment to the normal nondividing neural cells.

¹ This investigation was supported by Grants IN-36 from the American Cancer Society and R01-HD-07464 and P01-NS-14834 from the NIH.

² To whom requests for reprints should be addressed, at Division of Pediatric Neurology, Department of Neurology, College of Physicians and Surgeons of Columbia University, 710 West 168th Street, New York, N. Y. 10032.

Received 4/ 8/81. Accepted 6/ 2/81.