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Membrane effects of tumor promoters: Stimulation of sugar uptake in mammalian cell cultures

✍ Scribed by Lih-Syng Lee; I. Bernard Weinstein

Publisher
John Wiley and Sons
Year
1979
Tongue
English
Weight
838 KB
Volume
99
Category
Article
ISSN
0021-9541

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✦ Synopsis

Abstract

Phorbol esters stimulate 2‐deoxy‐D‐glucose (DG) uptake in rodent and human cell cultures. The potent tumor promoting agent, 12‐0‐tetradecanoyl phorbol‐13 acetate (TPA), induces a 12‐fold stimulation in confluent 3T3 cells and a 2.5‐fold stimulation in HeLa cells. When a series of macrocyclic diterpenes are assayed, their relative potencies in stimulating DG uptake in 3T3 cells correlate with other known biologic effects of these compounds. On a molar basis, TPA is a much more potent stimulator of DG transport than insulin or epidermal growth factor. In HeLa cells, the ED~50~ value of the TPA effect is 0.2 nM. The increase in DG uptake occurs immediately after the addition of TPA, reaches a maximum at 90 minutes, persists for at least three hours after removal of TPA from the medium, and is temperature dependent. The stimulation is not inhibited by cycloheximide or actinomycin D. As in control cells, DG uptake in TPA treated cells is inhibited by p‐hydroxymercuribenzoate, phloridzin, cytochalasin B, and dexamethasone. Although the precise mechanism is not known, evidence is presented that the TPA stimulation of DG uptake is due to enhanced transport of the sugar rather than to effects of intracellular metabolism. The enhanced transport may be secondary to a more generalized change in membrane structure.

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