4-[3,5-Bis(trimethylsilyl)benzamido] benzoic acid (TAC-101) inhibits the intrahepatic spread of hepatocellular carcinoma and prolongs the life-span of tumor-bearing animals.

Clinical & experimental metastasis ·Vol. 16 ·No. 7 ·1998-10-00 ·Pages 633-43

Murakami K, Matsuura T, Sano M, Hashimoto A, Yonekura K, Sakukawa R, Yamada Y, Saiki I

Abstract

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.

MeSH Terms

Animals Antineoplastic Agents/pharmacology Antineoplastic Agents, Phytogenic/pharmacology Apoptosis/drug effects Benzoates/pharmacology,toxicity Body Weight/drug effects Camptothecin/analogs & derivatives,pharmacology Carcinoma, Hepatocellular/drug therapy,mortality,pathology Fluorouracil/pharmacology Humans Irinotecan Liver Neoplasms/drug therapy,mortality,pathology Liver Neoplasms, Experimental/drug therapy,mortality,pathology Male Mice Mice, Nude Molecular Structure Neoplasm Invasiveness/prevention & control Proto-Oncogene Proteins c-met/metabolism Receptors, Retinoic Acid/metabolism Reverse Transcriptase Polymerase Chain Reaction Specific Pathogen-Free Organisms Survival Rate Trimethylsilyl Compounds/pharmacology,toxicity Tumor Cells, Cultured

Chemicals

Antineoplastic Agents Antineoplastic Agents, Phytogenic Benzoates Receptors, Retinoic Acid TAC 101 Trimethylsilyl Compounds Irinotecan Proto-Oncogene Proteins c-met Fluorouracil Camptothecin

Authors & Affiliations

8 authors, click to expand affiliations / ORCID

Murakami K

Department of Pathogenic Biochemistry, Research Institute for Wakan-Yaku, Toyama Medical and Pharmaceutical University, Japan. komuraka@hanno.taiho.co.jp

Matsuura T

Sano M

Hashimoto A

Yonekura K

Sakukawa R

Yamada Y

Saiki I

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Article Info

Journal

Clinical & experimental metastasis

Abbr.

Clin Exp Metastasis

ISSN

0262-0898

DOI

10.1023/a:1006567229929

komuraka@hanno.taiho.co.jp

Published

1998-10-00

Pages

633-43

Language

English

Region

Netherlands

NLM ID

8409970

Subset

External Links

PubMed source DOI: 10.1023/a:1006567229929 View journal details

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4-[3,5-Bis(trimethylsilyl)benzamido] benzoic acid (TAC-101) inhibits the intrahepatic spread of hepatocellular carcinoma and prolongs the life-span of tumor-bearing animals.

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