Interleukin 1 promotes tumor cell adhesion to cultured human endothelial cells.

We report that IL 1 acts on the endothelium, inducing a long-lasting increase in its adhesivity to tumor cells. Selective pretreatment of cultured human umbilical vein endothelial cells (EC) with IL 1 caused a significant increase in adhesion of three human colorectal carcinoma (HT-29, HCC-P2988, and HCC-M1410) cell lines and one human melanoma (A-375) cell line. Tumor necrosis factor (TNF) was as effective as IL 1 in promoting tumor cell adhesion to EC, whereas IFN gamma and IL 2 were inactive. The IL 1 and TNF induction of EC adhesivity was both concentration (threshold concentration 1 U/ml) and time dependent (peak 4-6 h), reversible within 24 h, and blocked by a protein synthesis inhibitor. The IL 1 and TNF action on EC may play a role in tumor cell lodgement.

Antiproliferative properties of flavone acetic acid (NSC 347512) (LM 975), a new anticancer agent.

The antiproliferative activity of flavone acetic acid (LM 975) was investigated on human adenocarcinoma cell lines (HCC-P2998, HCC-M1544, HCC-M1410, HT 29, LoVo), on a murine colon adenocarcinoma cell line (Colon 26), on murine pancreatic adenocarcinoma cells growing in primary culture (Pan 03) and on human normal fibroblasts (N1). No cytotoxic effects were found against human normal fibroblasts. LM 975 was active against murine adenocarcinoma Pan 03 and Colon 26, known to be sensitive in vivo too and, to variable extents, on human adenocarcinoma cell lines. LM 975 in vitro cytotoxic potency was relatively low. The high concentrations (1.0-1.4 mM) required to obtain a cytotoxic effect are, however, pharmacologically reasonable since they are comparable with drug plasma levels in mice or in patients treated with tolerable doses. After a relatively short LM 975 treatment (2 h) DNA, RNA and protein synthesis were inhibited in different proportions. In more sensitive cells LM 975 appeared to inhibit RNA synthesis more than DNA and protein synthesis. Inhibition of macromolecule synthesis after 2 h exposure was completely reversed in 24 h recovery. After 2 h treatment no detectable DNA breakage was found by the alkaline elution method, thus corroborating the idea that this compound does not act by causing DNA damage.