Gamma linolenic acid alters the cytotoxic activity of anticancer drugs on cultured human neuroblastoma cells.
Gamma linolenic acid (GLA) by itself shows anti-tumor activity on various neoplastic cells in culture. We investigated the combined effect of GLA and anticancer drugs on two human neuroblastoma cell lines. The cytotoxic effect of Vinca alkaloids such as vincristine (VCR), vindesine (VDS) and vinblastine (VBL) was about 2-fold enhanced when GLA was added simultaneously to the growth medium. On the other hand, that of platinating agents such as cisplatin (CDDP) and carboplatin (CBDCA) was inhibited by GLA supplementation. The cytotoxic activity of other anticancer agents was not affected by GLA. Pharmacokinetic studies on VCR and CDDP demonstrated that intracellular accumulation of [3H]-VCR was about 1.5-fold increased in the cells pretreated by GLA, while, on the contrary, that of CDDP was rather decreased; cellular efflux of either drug was not affected. Malon dialdehyde (MDA) formation induced by supplemented GLA was not influenced by either VCR or CDDP. These results indicate that GLA exerts differential effects on the kinetics of anticancer drugs.
Ikushima
S
S
Department of Pediatrics, Children's Research Hospital, Kyoto Prefectual University of Medicine, Japan.
Fujiwara
F
F
Todo
S
S
Imashuku
S
S
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000493:pharmacokinetics; D006801:Humans; D008042:Linolenic Acids / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D009447:Neuroblastoma / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014750:Vincristine / Q000493:pharmacokinetics; D017965:gamma-Linolenic Acid
D000970:Antineoplastic Agents; D008042:Linolenic Acids; D014750:Vincristine; D017965:gamma-Linolenic Acid; D002945:Cisplatin