A novel immunosuppressive drug, FTY720, prevents the cancer progression induced by cyclosporine.
Cyclosporine A (CsA), the most frequently used immunosuppressive drug, has been reported to induce cancer by a cell-autonomous mechanism. Herein, we report that FTY720, a novel immunosuppressant, prevents CsA-induced alterations in both morphology and cell motility at a low concentration (0.1 microM) and induces the CsA-treated cancer cells to undergo apoptosis at a higher concentration (more than 5 microM). The inhibitory activity of FTY720 is unrelated to the decrease of TGF-beta. We believe that a combination treatment with FTY720 and CsA not only results in a synergistic effect on allografts, but also, reduces the incidence of cancer in transplant patients.
Tanaka
Toshiyuki
T
Department of Urology, Gunma University School of Medicine, Maebashi, Gunma, Japan.
Takahara
Shiro
S
Hatori
Motoaki
M
Suzuki
Kazuhiro
K
Wang
Jing
J
Ichimaru
Naotsugu
N
Suzuki
Seiichi
S
Morozumi
Kunio
K
Okuyama
Akihiko
A
Yamanaka
Hidetoshi
H
D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D016572:Cyclosporine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D011409:Propylene Glycols / Q000494:pharmacology*; D013110:Sphingosine / Q000031:analogs & derivatives; D016212:Transforming Growth Factor beta / Q000502:physiology; D014407:Tumor Cells, Cultured
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D016212:Transforming Growth Factor beta; D016572:Cyclosporine; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine