Since the late 1970s, a comprehensive search for
cancer chemopreventive agents has been established in our Institute. A series of new
retinoids have been synthesized and screened on the basis of established methodologies of experimental
chemoprevention in vitro as well as in vivo. Pharmacological studies demonstrated that N-4-(carboxyphenyl)retinamide (RII) induces cell differentiation of HL-60 cells and inhibits
dimethylnitrosamine-induced
carcinogenesis of the forestomach in mice, 7,12-dimethylbenz[a]
anthracene (DMBA)-induced
papilloma in mouse skin, and DMBA-induced
carcinogenesis of the buccal pouch in Syrian golden hamsters. It significantly promoted lymphoblastic transformation and activated macrophages. In further studies, RII significantly inhibited
ornithine decarboxylase activity. After 6 months of chronic toxicological studies in rats and dogs, RII was recommended for clinical trial. Phase II studies found that RII is effective in treating oral and vulvar
leukoplakia. It is also effective in treating
myelodysplastic syndrome and dysplasia of uterine cervix. The
chalcone retinoidal compounds were discovered when the search for new
retinoids with less toxicity and higher potency led to third-generation
retinoids, which were synthesized and screened. Structure-activity relationship studies found that 3,5-di-tert-butyl-4-methoxy-4-carboxyl
chalcone (
R9158) is the most active inhibitor of a variety of
cancer cells. It has no effect on the Colony Forming Unit-Granulocyte/Macrophage (CFU-GM) of bone marrow in mice. In in vivo studies,
R9158 showed a remarkable inhibition of
chondrosarcoma in rats. It had no cross-resistance to
vincristine, but was cross-resistant to
all-trans retinoic acid. Red ginseng, a processed Panax ginseng, is considered a typical tonic in
traditional Chinese medicine. Our studies demonstrated that red ginseng extract inhibited DMBA-induced skin
papilloma significantly. Experiments showed that
glycyrrhetinic acid inhibited
croton oil-induced ear
edema in mice. It also inhibited epidermal
ornithine decarboxylase as well as the rapid DNA damage induced by the
carcinogen benzo[a]pyrene (B[a]P). Our pharmacological studies demonstrated that Chinese
gallotannin inhibited the malignant transformation of B[a]P-induced V79 cells in vitro and B[a]P-induced pulmonary
adenoma in A/J mice in vivo significantly.