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.
Laboratory of Pathologie Cellulaire, Institut de Recherches Scientifiques sur le Cancer (IRSC), CNRS, Villejuif, France.
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IM
Bennani-Baiti
C
C
Lafarge-Frayssinet
J
J
Herscovici
R
R
Monserret
S
S
Robbana-Barnat
K
K
Antonakis
C
C
Frayssinet
J
J
Uriel
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology; D001854:Bone Marrow Cells; D002945:Cisplatin / Q000494:pharmacology / Q000633:toxicity; D004317:Doxorubicin / Q000494:pharmacology / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000494:pharmacology / Q000633:toxicity; D005472:Fluorouracil / Q000494:pharmacology / Q000633:toxicity; D006027:Glycosides / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D007165:Immunosuppression Therapy; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D011753:Pyrones / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344
D000970:Antineoplastic Agents; D006027:Glycosides; D011753:Pyrones; D005047:Etoposide; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil