The effects of the non-12-O-tetradecanoylphorbol-13-acetate type
tumor promoter palytoxin on human bronchial epithelial cells was studied in an in vitro serum-free culture system. Unlike the results of previous studies with another
tumor promoter, 12-O-tetradecanoylphorbol-13-acetate,
palytoxin did not induce squamous differentiation of normal bronchial epithelial cells and was equally cytotoxic for normal human bronchial epithelial cells, a human lung tumor cell line, and human bronchial epithelial cells immortalized by
infection with adenovirus 12-SV40 hybrid virus (BEAS-2B cells).
Palytoxin did not induce a change in free cytosolic Ca2+ concentration of BEAS-2B cells. The effect of
palytoxin on the c-myc
mRNA steady state level in BEAS-2B cells was studied: 1 pM
palytoxin increased the steady-state level at 12 and 18 h. Furthermore, the induction was accompanied by an increase in [3H]
thymidine uptake. Because
palytoxin binds to (Na+ + K+)
ATPase, the effects of
ouabain were compared to the effects of
palytoxin. A
ouabain-resistant cell line was as sensitive to the growth inhibitory effect of
palytoxin as the parent
ouabain-sensitive cell line, suggesting different binding sites to the (Na+ + K+)-
ATPase for
palytoxin and
ouabain.
Ouabain also increased the steady-state level of c-myc gene expression, but earlier than
palytoxin, and the increase in the level of c-myc
mRNA was accompanied by a drop in
DNA synthesis. These results suggest that
palytoxin does not act by growth stimulation, differential cytotoxicity or terminal differentiation of normal versus neoplastic cells which are proposed mechanisms of
tumor promotion.