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Anti‐tumor activity of ceramides and glycosphingolipids in a murine tumor system
Author(s) -
Maru Morimasa,
Haraguchi Muneo,
Higashi Hideyoshi,
Kato Shiro,
Kurimura Takashi,
Naiki Masaharu,
Wakamiya Nobutaka
Publication year - 1993
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910530420
Subject(s) - ceramide , sphingolipid , in vivo , immune system , cytotoxic t cell , antibody , tumor necrosis factor alpha , cytotoxicity , cancer research , chemistry , pharmacology , biology , in vitro , endocrinology , medicine , biochemistry , immunology , apoptosis , microbiology and biotechnology
The anti‐tumor activity of 7 sphingolipids, 2 ceramides and 5 glycosphingolipids against the syngeneic murine ascitic tumors MH 134 and MM 102 in C3H mice was examined. Five of these compounds showed anti‐tumor activity against the tumors, ceramide type‐IV (Cer‐lv) 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 (MH 134 → MH134, MM102 → MM102) but not with a heterologous tumor (MH 134 → 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 TNFα) in the induction phase (before Cer‐IV administration) and by the antibodies of L3T4 and TNFα 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.