Positive Health Online

Abstract

RUI, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, People's Republic of China writes that a comprehensive search for cancer chemopreventive agents was established at their Institute since the late 1970s.

Background

Methodology

Results

A series of new retinoids (derived from vitamin A) have been synthesised and screened . Pharmacological studies demonstrated that N-4-(carboxyphenyl)retinamide (RII) induces cell differentiation of HL-60 cells and inhibits dimethylnitro- samine-induced carcinogenesis of the forestomach in mice, 7,12-dimethylbenz(a)anthracene (DMBA)-induced papilloma in mouse skin, and DMBA-induced cancer of the buccal pouch in Syrian golden hamsters. RII significantly promoted lymphoblastic transformation and activated macrophages and significantly inhibited ornithine decarboxylase activity. Following 6 months of chronic toxicity studies, RII was recommended for clinical trials in humans. Phase II studies demonstrated RII's efficacy in the treatment of oral and vulvar leukoplakia as well as myelodysplastic syndrome and dysplasia of the uterine cervix . Chalcone retinoidal compounds were discovered in the search for new retinoids with less toxicity and higher potency, which led to third-generation retinoids. Structure-activity relationship studies of these compounds discovered that 3,5-ditert-butyl-4- methoxy-4-carboxyl chalcone (R9158) is the most active inhibitor of a variety of cancer cells, although it has no effect upon the Colony Forming Unit-Granulocyte/Macrophage (CFU-GM) of bone marrow in mice. In vivo studies demonstrated that R9158 showed remarkable inhibition of chondrosarcoma in rats, had no cross-resistance to vincristine, but was cross-resistant to all-trans retinoic acid. Red ginseng, a processed Panax ginseng, which is considered a typical tonic in traditional Chinese medicine, significantly inhibited DMBA- induced skin papilloma. Glycyrrhetinic acid inhibited croton oil-induced ear oedema in mice and inhibited epidermal ornithine decarboxylase and rapid DNA damage induced by benzo(a)pyrene (B(a)P). 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 mice in vivo significantly.

Conclusion

A variety of chemopreventive agents have been developed in China and have been shown to exhibit a range of anti-cancer activity.

References

Rui H. Research and development of cancer chemopreventive agents in China. J Cell Biochem Suppl 27: 7-11. 1997.

Comment

The above study summarises two decades of research from one China Institute in the development of anti-cancer agents from vitamin A compounds and from Chinese medicinal herbs such as Ginseng. It is clear that this work has progressed from cell culture and animal studies to human clinical trials and that positive, tangible results will result in the development of specific anti-cancer agents.