Double screening of suramin derivatives on human colon cancer cells and on neural cells provides new therapeutic agents with reduced toxicity.
Suramin is a polyanionic compound currently used under evaluation for antineoplastic activity. One of the main problems encountered during clinical trials was an adverse neurotoxic effect, probably due to a direct cytotoxic effect on neural cells. Suramin is also known to trigger differentiation of human colon cancer cells, yet a chronic treatment induces a lysosomal storage disorder. The aim of this study was to evaluate suramin analogs for their effect: (i) on the lysosomal system of the human colon cancer cell clone HT29-D4; and (ii) on C6 glioma cell growth and morphology. One of the derivatives tested, NF036, induced terminal differentiation of HT29-D4 cells without any impairment of the lysosomal system. Furthermore, in contrast to suramin, NF036 did not alter C6 cell growth and morphology. We conclude that there is a relationship between the ability of a suramin derivative to induce a lysosomal storage disorder in human colon cancer cells and its neurotoxic effect. A double screening of suramin analogs on HT29-D4 and C6 cells allowed us to identify a new candidate antineoplastic drug: NF036.
Baghdiguian
S
S
INSERM U270, Faculty of Médicine, Marseille, France.
Nickel
P
P
Fantini
J
J
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D003110:Colonic Neoplasms; D004354:Drug Screening Assays, Antitumor; D005910:Glioma; D006801:Humans; D007700:Kinetics; D008247:Lysosomes / Q000187:drug effects / Q000648:ultrastructure*; D013329:Structure-Activity Relationship; D013498:Suramin / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D013498:Suramin