Anti-tumor activity of ceramides and glycosphingolipids in a murine tumor system.
The anti-tumor activity of 7 sphingolipids, 2 ceramides and 5 glycosphingolipids against the syngeneic murine ascitic tumors MH134 and MM102 in C3H mice was examined. Five of these compounds showed anti-tumor activity against the tumors, ceramide type-IV (Cer-IV) having the highest activity without cytotoxic or cytostatic activity. These results indicate that the fatty acid in ceramide and sugar chains binding to it affect the anti-tumor activity in vivo. The anti-tumor activity of Cer-IV depended on the time of treatment. Mice treated with Cer-IV one day after tumor implantation showed the highest rate of survival. The cured mice were resistant to rechallenge with the same tumor (MH134-->MH134, MM102-->MM102) but not with a heterologous tumor (MH134-->X5563, MM102-->X5563), indicating that the effect of Cer-IV may be due to in vivo induction of specific immunity. Studies with various antibodies demonstrated that the anti-tumor effect of Cer-IV was inhibited by all the antibodies tested (L3T4, Lyt-2, and Thy-1,2 T cells, macrophages, and TNF alpha) in the induction phase (before Cer-IV administration) and by the antibodies of L3T4 and TNF alpha in the effector phase (after Cer-IV administration). Therefore, the anti-tumor effect of Cer-IV in this system depended on the host immune response rather than on its direct cytotoxic and/or cytostatic action.
Maru
M
M
Shionogi Research Laboratories, Shionogi and Co., Ltd., Osaka, Japan.
Haraguchi
M
M
Higashi
H
H
Kato
S
S
Kurimura
T
T
Naiki
M
M
Wakamiya
N
N
D000818:Animals; D000970:Antineoplastic Agents; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002518:Ceramides / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D006028:Glycosphingolipids / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002518:Ceramides; D006028:Glycosphingolipids