Biochemical and Morphological Study of Adriamycin-Induced Changes in Murine Neuroblastoma Cells

Abstract

Cholinergic murine neuroblastoma cells, maintained in vitro, were exposed to a low concentration (0.4 μg/ml) of adriamycin. Morphologically the treated cells appeared to differentiate. The cell bodies increased in size from an average fixed cell body diameter of 7–13 to 25–40 μm, the cells developed long processes, became argyrophilic and the percentage of cells undergoing mitosis decreased relative to controls. Acetylcholine esterase activity increased in the drug-treated cells suggesting induction of differentiation. However, choline acetyltransferase activity and ganglioside composition remained unchanged. In addition, inoculation of mice with 2 × 10⁵ viable drug-treated or control cells resulted in all of the mice developing neuroblastoma. No differences were observed in either the rate of tumor development or survival times. These results suggest that neuroblastoma cells may survive adriamycin treatment by becoming ‘differentiated’, ceasing cell division until conditions favor their undergoing another cell cycle.

Density‐Dependent Changes in Gangliosides and Sialidase Activity of Murine Neuroblastoma Cells

“…In this work, the ganglioside composition, exposed sialyl residues, and membrane-associated sialidase activity were determined for murine neuroblastoma cells at different cell densities to ascertain whether they underwent alterations that might be related to changes in rate of cell division or the expression of properties associated with differentiated neurons. 94 I and maintained as previously described (Schengrund and Sheffler, 1982), except that 10% donor calf serum was used in place of fetal calf serum. Cells were harvested by rapping and seeded at a density of 5 x 1 0 viable cells per 75-cm' flask.…”

A Mechanistic Study of Doxorubician/Adriamycin's Effect on the Estrogen Response in a Breast Cancer Model

“…Additionally, studies in ER-breast carcinoma, melanoma, and fibrosarcoma models have shown that doxorubicin can impair migration and invasion, and this may occur through the negative regulation of FAK and Rho activity (Fourre et al, 2008;Millerot-Serrurot et al, 2010;Pichot et al, 2009;Repesh et al, 1993). Interestingly, an in vitro study in murine neuroblastoma revealed that doxorubicin induced the partial differentiation of cancer cells in that system (Schengrund and Sheffler, 1982). The negative impact of doxorubicin on ER+ breast cancer cell lines, such as decreased cell viability (Fornari et al, 1994), apoptotic induction (Sharma et al, 2004), and cell cycle arrest (Janicke et al, 2001; Rusetskaya et al, 2009), contrast with the positive influences of estrogen on these biological processes.…”