am-555s and Body-Weight

We examined the in vivo anti-tumor activity of the benzoic acid derivative, TAC-101 (4-[3,5-bis(trimethylsilyl)benzamido] benzoic acid), for intrahepatic spread of JHH-7 human hepatocellular carcinoma (HCC) cells and its mechanism of action. Oral administration of TAC-101 markedly inhibited liver tumor of JHH-7 cells and prolonged the life-span of tumor-bearing mice without affecting the body weight. The life-prolonging effect of TAC-101 was more effective than that of other anti-cancer agents including CDDP, 5-FU, and CPT-11 (T/C (%) of life-span; 181 to 219, 128, 133, and 142%, respectively). In vitro, TAC-101 at the concentration of more than 10 microM showed direct cytotoxicity against JHH-7 cells caused by induction of apoptosis. Hepatocyte growth factor (HGF) enhanced the invasive ability of JHH-7 cells without affecting the cell viability. Non-cytotoxic concentrations of TAC-101 inhibited the JHH-7 invasion induced by HGF and down-regulated the expression of c-MET protein in a concentration-dependent manner. In summary, these results suggest that TAC-101 would be useful for a new class of therapeutic agents and that it may improve the prognosis of patients with liver-tumors including metastasizing tumor and HCC.

Topics: Animals; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Apoptosis; Benzoates; Body Weight; Camptothecin; Carcinoma, Hepatocellular; Fluorouracil; Humans; Irinotecan; Liver Neoplasms; Liver Neoplasms, Experimental; Male; Mice; Mice, Nude; Molecular Structure; Neoplasm Invasiveness; Proto-Oncogene Proteins c-met; Receptors, Retinoic Acid; Reverse Transcriptase Polymerase Chain Reaction; Specific Pathogen-Free Organisms; Survival Rate; Trimethylsilyl Compounds; Tumor Cells, Cultured