Interaction of delta-9-tetrahydrocannabinol with rat B103 neuroblastoma cells

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Abstract
The effect of delta-9-tetrahydrocannabinol (delta-9-THC) on the growth kinetics and morphology of rat B103 neuroblastoma cells was assessed. Delta-9-THC in doses ranging from 10−4 to 10−7 M inhibited cellular growth in a dose-dependent fashion as evidenced by delay in doubling time, decrease in saturation density, and decrease in efficiency of plating. The inhibition in cellular growth was paralleled by dose-related alterations in cell morphology. Modifications included rounding of cells, retraction of neurites, blebbing of the cell surface, and exfoliation of the plasma membrane. Cytoplasmic alterations included distension of the endoplasmic reticulum, Golgi apparatus, and perinuclear space, and macrovacuolization. Intracytoplasmic laminated inclusions and vesicular clusters were suggestive of membrane repair in drug-treated cells. These morphological changes were accompanied by cytoskeletal rearrangement in the absence of significant alteration in the concentration of total cytoskeletal protein. Autoradiographic examination of the intracellular fate of 3H-delta-9-THC demonstrated that the drug was confined to the cytoplasmic compartment and often associated with macrovacuoles. These results suggest that delta-9-THC interacts with cellular membranes, thereby altering neuroblastoma cell growth and behavior.