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Retinoids prevent epithelial carcinogenesis induced by N-nitroso compounds
1Cancer Institute, Sun Yat-Sen University of Medical Sciences, Guangzhou, China.
IARC Scientific Publications
|January 1, 1991
Summary
Two novel retinamides, RI and RII, effectively inhibited chemical-induced carcinogenesis in mouse and rat models. These compounds also demonstrated anti-cancer effects in vitro without signs of toxicity, suggesting therapeutic potential.
Area of Science:
- Oncology
- Medicinal Chemistry
- Carcinogenesis Research
Background:
- Chemical carcinogens like N-nitrososarcosine ethyl ester and dinitrosopiperazine induce precancerous and cancerous lesions in various organs.
- Retinoids are known for their role in cell differentiation and cancer prevention, necessitating the development of novel analogs.
Purpose of the Study:
- To synthesize and evaluate the anti-cancer properties of two new retinamides, N-(4-ethoxycarbophenyl)retinamide (RI) and N-(4-carboxyphenyl)retinamide (RII).
- To assess the efficacy of RI and RII in inhibiting chemically induced carcinogenesis in animal models and their effects on cancer cell lines.
Main Methods:
- Synthesis of novel retinamides RI and RII.
- Administration of RI and RII to mice and rats exposed to chemical carcinogens (N-nitrososarcosine ethyl ester, dinitrosopiperazine).
- In vitro studies using a rat malignant oesophageal epithelial cell line (RE25-3) to assess effects on cell division, DNA synthesis, and colony formation.
Main Results:
- RI and RII significantly inhibited forestomach carcinogenesis in mice induced by N-nitrososarcosine ethyl ester.
- RI markedly inhibited oesophageal and forestomach carcinogenesis in rats induced by the same ester.
- RI also inhibited precancerous and cancerous lesions in the nasal cavity, nasopharynx, and oesophagus of rats induced by dinitrosopiperazine.
- Both RI and RII inhibited mitosis, proliferation, chromosomal aberrations, and DNA synthesis in the RE25-3 cell line.
- Colony formation ability was also inhibited by RI and RII in vitro.
- No signs of hypervitaminosis were observed even at doses six times the therapeutic level.
Conclusions:
- N-(4-ethoxycarbophenyl)retinamide (RI) and N-(4-carboxyphenyl)retinamide (RII) are potent inhibitors of chemical carcinogenesis in vivo.
- These novel retinamides exhibit anti-proliferative and anti-clastogenic effects on cancer cells in vitro.
- RI and RII show promise as chemopreventive or therapeutic agents against various cancers with a favorable safety profile.