Rm. Schultz et al., IN-VITRO AND IN-VIVO ANTITUMOR-ACTIVITY OF THE PHOSPHATIDYLINOSITOL-3-KINASE INHIBITOR, WORTMANNIN, Anticancer research, 15(4), 1995, pp. 1135-1139
The microbial product wortmannin has previously been shown to be a pot
ent inhibitor of phosphatidylinositol-3-kinase. In view of the potenti
al role of this enzyme in transduction of mitogenic signals, we determ
ined the cytotoxic activity of wortmannin against several human tumor
cell lines in vitro. The most sensitive lines included GC3 colon carci
noma, IGROV1 ovarian carcinoma, and CCRF-CEM leukemia (IC-50s ranging
from 0.7-2. 1 mu M) The cytotoxicity of wortmannin was decreased appro
ximately 10-fold by serum-free conditions Wortmannin was generally les
s active in low passage human breast cancer cell lines that overexpres
s either epidermal growth factor receptor ol Her2/neu. Wortmannin was
also tested for in vivo antitumor activity against seven murine tumor
and ten human tumor xenograft models. Activity (>60% inhibition of tum
or. growth) was observed in only the C3H mammary carcinoma and the hum
an BxPC-3 pancreatic carcinoma xenograft. In vivo antitumor activity d
id not correlate with in vitro sensitivity to wortmannin cytotoxicity.