In vitro evaluation of the differential cytotoxicity of keto-C-glycosides toward normal and malignant cells.

In a previous work, we have shown that some members of the family of keto-C-glycosides (KCGs) possess interesting biological properties as they exhibited cytotoxic effects at the nanomolar level on malignant cells. In this report, we selected six KCGs in order to investigate their selective cytotoxicity on several malignant epithelial and lymphoblastoid cells, as well as on their normal counterparts. For this purpose, we compared the activities of KCGs upon hepatoma cells and hepatocytes and upon lymphoma cells, normal lymphocytes and bone marrow cells. The tested drugs showed real discriminating cytotoxic effects since the cytotoxicity was several log greater on malignant than on non malignant cells. An in vitro comparative study of KCGs and some conventional chemotherapeutic agents showed that two of them were more potent than 5-fluorouracil, cis-platinum and etoposide. It is interesting to note that KCGs showed very low cytotoxic effects on either murine splenocytes, human peripheral blood lymphocytes or human bone marrow cells, indicating a weak immunosuppressive activity. The results presented here strongly suggest the selective cytotoxic activity of KCGs toward tumoral cells.

Potential antineoplastic activity of keto-C-glycosides--a new family of cytostatic agents.

We have examined the biological activity of keto-C-glycosides (KCGs), a new family of drugs displaying antiproliferative and cytotoxic properties on tumor cells. KCG1, the most powerful drug tested on epithelial derived neoplastic cells, was 25-125 times more cytostatic on epithelial cells than on lymphoma. By contrast, KCG10 proved to be more cytostatic on lymphoma than on epithelial cells. Correlations were found between the cytostaticity of KCGs and their lipophilicity, and are discussed within the framework of the structure-activity and the structure-selectivity relationships.