title: Cinnamamide, an antitumor agent with low cytotoxicity acting on matrix metalloproteinase.
abstract: The antitumor activity of cinnamamide (CNM), an agent acting on matrix metalloproteinase (MMP), was investigated in the present study. CNM displayed low cytotoxicity. By the MTT assay the IC50 (50% inhibitory concentration) values of CNM on cell proliferation ranged from 1.29 to 1.94 mM in human oral epidermoid carcinoma KB cells, human hepatoma BEL-7402 cells and human fibrosarcoma HT-1080 cells. Moreover, the IC50 for human fetal lung 2BS cells reached 4.33 mM. The administration of CNM in the range of 50-150 mg/kg (i.p. or p.o.) showed moderate antitumor effects in mice. When administered i.p. or p.o., CNM (150 mg/kg) inhibited the growth of transplanted hepatoma 22 by 48.8 or 40.5%, respectively. At the dose of 100 mg/kg, CNM inhibited the growth of colon 26 carcinoma by 39.0% and that of Lewis lung carcinoma by 53.9%. In the Lewis lung carcinoma model, CNM at the dose of 100 mg/kg (i.p.) also reduced the lung metastasis by 59.1%. Gelatine zymography revealed that CNM was able to decrease the level of MMP-2 in conditioned medium of HT-1080 tumor cells in a concentration-dependent manner. These results indicate that CNM is an antitumor agent with low cytotoxicity acting on MMP and may serve as a lead compound in the development of antitumor drugs.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.
authors.forename: X
authors.initials: X
authors.lastname: Jiang
authors.forename: Y
authors.initials: Y
authors.lastname: Zhen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002934:Cinnamates / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D007624:KB Cells; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000556:secondary; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002934:Cinnamates; D020778:Matrix Metalloproteinase 2; C411088:cinnamamide