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Membrane effects of tumor promoters: Stimulation of sugar uptake in mammalian cell cultures
Author(s) -
Lee LihSyng,
Weinstein I. Bernard
Publication year - 1979
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1040990319
Subject(s) - cycloheximide , stimulation , cytochalasin b , intracellular , tetradecanoylphorbol acetate , hela , cell culture , phloretin , phorbol , cell , biochemistry , cytochalasin , chemistry , biology , microbiology and biotechnology , protein biosynthesis , endocrinology , protein kinase c , cytoskeleton , phosphorylation , genetics
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.