Antiproliferative effects of amphiphilic molecules.
Previous investigations indicated that certain long chain amphiphiles possess immunosuppressive activity. Here we tested this concept by studying the ability of a series of nitrogen-containing amphiphiles of varying hydrocarbon chain lengths to inhibit the human mixed lymphocyte reaction (MLR). Seventeen of 29 compounds were classified as inhibitory in the MLR but not toxic to the cells, six were both inhibitory and toxic to the cells, and six were inactive at the concentrations tested. In contrast, cyclosporin A inhibited the MLR and was not toxic. With the hypothesis that the amphiphiles might act to inhibit cell proliferation in a nonspecific manner, they were tested on a battery of tumor cell lines at concentrations that did not show toxicity in the MLR. Whereas cyclosporin A did not inhibit the proliferation of tumor cells, most of the active amphiphiles did inhibit tumor cell proliferation and, in addition, killed the tumor cells. These results suggest that the amphiphiles are antiproliferative and do not show specificity of action on cells of the immune system. Finally, based on available data that showed poor skin penetration, no significant human health risk seems likely from skin contact with these chemicals, as they are currently used in household products or rinse-off personal care products.
Coy
E A
EA
Department of Immunology, Mayo Clinic, Rochester, MN 55095.
Reddy
A K
AK
Hostynek
J J
JJ
Gleich
G J
GJ
D000328:Adult; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D013501:Surface-Active Agents / Q000494:pharmacology* / Q000633:toxicity; D014407:Tumor Cells, Cultured / Q000187:drug effects
D007166:Immunosuppressive Agents; D013501:Surface-Active Agents