Induction of tumor necrosis factor by a camptothecin derivative, irinotecan, in mice and human mononuclear cells.
Irinotecan (CPT-11) has been reported to be cytotoxic to tumor cells through its inhibitory activity on type I DNA topoisomerase. CPT-11 has also been shown to have several unique biological activities apart from direct cytotoxicity. We investigated the ability of CPT-11 to induce tumor necrosis factor (TNF) production. Human peripheral blood mononuclear cells (MNCs) were incubated with LPS, CPT-11, or with vinblastin sulfate as a control. The priming effect of CPT-11 on endogenous production of TNF was examined by injecting the drug intravenously into mice, followed 3 hours by the injection of OK432. At a dose of 200-400 micrograms/kg, CPT-11 showed a significant priming effect. A significant amount of TNF was released when MNCs were incubated with 100-300 microM of CPT-11 for more than 4 hours, but not with vinblastin sulfate, indicating a triggering effect of TNF production on MNCs in vitro. These effects may be advantageous in cancer therapy.
Goto
S
S
Biotechnology Research Center, Teikyo University, Kanagawa, Japan.
Okutomi
T
T
Suma
Y
Y
Kera
J
J
Soma
G
G
Takeuchi
S
S
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D000077146:Irinotecan; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000972:Antineoplastic Agents, Phytogenic; D014409:Tumor Necrosis Factor-alpha; D000077146:Irinotecan; D002166:Camptothecin