mRNA levels of related Abcb genes change opposite to each other upon histone deacetylase inhibition in drug-resistant rat hepatoma cells.

The multidrug-resistant phenotype of tumor cells is acquired via an increased capability of drug efflux by ABC transporters and causes serious problems in cancer treatment. With the aim to uncover whether changes induced by epigenetic mechanisms in the expression level of drug transporter genes correlates with changes in the drug resistance phenotypes of resistant cells, we studied the expression of drug transporters in rat hepatoma cell lines. We found that of the three major rat ABC transporter genes Abcb1a, Abcb1b and Abcc1 the activity of only Abcb1b increased significantly in colchicine-selected, drug-resistant cells.

Antiproliferative and apoptosis-inducing effects of hemin in hepatoma cells.

Hemin is an extremely versatile molecule that may have cytotoxic or cytoprotective effects on certain cells. We investigated the effect of hemin on the growth of hepatoma cells, including the multidrug-resistant ones. Searching for new tools that interfere with the growth of hepatomas is an important area of clinical research.

Sugar amino acid containing somatostatin analogues that induce apoptosis in both drug-sensitive and multidrug-resistant tumor cells.

[carbohydrate structure--see text] Resistance to chemotherapy has become a major problem in cancer therapy. The new sugar amino acid (SAA) containing somatostatin analogues presented possess antiproliferative and apoptotic activity against both multidrug-resistant and drug-sensitive hepatoma carcinoma cells. Synthesis, design, and biological evaluation of the cyclic analogues and of the furanoid SAA used will be discussed.

Novel lipoamino acid- and liposaccharide-based system for peptide delivery: application for oral administration of tumor-selective somatostatin analogues.

Lipoamino acid and liposaccharide conjugates of somatostatin analogue TT-232 were synthesized to modify the physicochemical properties of the parent peptide. The relative position, the number, and the nature of the lipid and/or saccharide moieties were varied. Experiments in vitro clearly showed that many compounds modified at the N- and/or C-terminus with lipid or sugar moieties retained the biological activity of the parent compound.

Apoptosis is induced in both drug-sensitive and multidrug-resistant hepatoma cells by somatostatin analogue TT-232.

Clinical resistance to chemotherapeutic drugs is an important problem in the treatment of cancer; the circumvention of resistance has become one of the basic goals of cancer therapy. The most frequent form of primary liver cancer is hepatocellular carcinoma, which is essentially refractory to chemotherapy. We earlier showed that TT-232, a new somatostatin analogue developed in our laboratory, exerted a strong antiproliferative effect both in vitro and in vivo, but no growth hormone release inhibitory or antisecretory activity.