n-(4-carboxyphenyl)retinamide and Stomach-Neoplasms

4-hydroxycarbophenyl retiamide (R II) is a new synthetic analogue of retinol, but with lower toxicity than retinoic acid. We studied its induction effects and its effects on some malignant phenotypes of the MFC cell line. The mechanism of these effects was also explored. MFC cells were grown in complete RPMI 1640 medium supplemented with 10(-5) mol/L R II for five passages. By then the cell growth rate slowed down; the rate of 3H-TdR incorporation and the colony-forming capacity of MFC cells decreased; morphologically, the cells became epithelial rather than fibroblastic with various degrees of polarization. Further investigation about the mechanism of these changes was also undergone. First by flow cytometry, it was shown that the R II-treated cells were retained in G1 phase. Second, dot blot hybridization showed a decrease of more than 61% of c-myc mRNA and an increase of more than 52% of v-fos mRNA. The major chromosome distribution changed from 54-56 to 46-54 with an increase in diploid. Scanning microscopic examination showed that the R II-treated cells were covered by numerous microvilli and pseudopodia with round terminal expansion in contrast to the ruffle protrusions and leaf-like pseudopodia of control cells. All the results suggested that R II could reverse some malignant phenotypes of MFC cells.

Topics: Animals; Antineoplastic Agents; Cell Transformation, Neoplastic; Gene Expression Regulation, Neoplastic; Genes, fos; Genes, myc; Mice; Mice, Inbred Strains; Phenotype; RNA, Messenger; Stomach Neoplasms; Tretinoin; Tumor Cells, Cultured

Two new retinoic acid esters and retinamides synthesized in China, N-(4-ethoxycarbophenyl)retinamide (RI) and N-(4-carboxyphenyl)retinamide (RII), significantly inhibited carcinogenesis induced in the epithelium of the forestomach of mice by N-nitrososarcosine ethyl ester. RI also markedly inhibited carcinogenesis induced in the epithelium of the oesophagus and forestomach in rats by this ester. No sign of hypervitaminosis was noticed with doses as high as six times the therapeutic dose. RI also inhibited precancerous and cancerous lesions in the nasal cavity and nasopharynx and oesophagus of rats induced by dinitrosopiperazine. In a malignant oesophageal epithelial cell line from rats, RE25-3, established in our laboratory, RI and RII inhibited mitosis, proliferation rate, chromosomal aberrations and incorporation of 3H-thymidine into DNA. The ability to form colonies on agar plates was also inhibited by these two compounds.

Topics: Animals; Antineoplastic Agents; Carcinogens; Esophageal Neoplasms; Female; Mice; Nitrosamines; Rats; Rats, Inbred Strains; Stomach Neoplasms; Tretinoin; Tumor Cells, Cultured