title: Use of curcumin to decrease nitric oxide production during the induction of antitumor responses by IL-2.
abstract: Nitric oxide (NO) synthesis is strongly induced during interleukin (IL)-2 treatment of mice and humans. Although this free radical can act as a cytotoxic effector molecule against cancer cells, immunosuppressive effects have also been suggested. We evaluated the effects of curcumin on IL-2-induced NO synthesis and IL-2-induced antitumor responses in a mouse ascites tumor model. Curcumin inhibited inducible nitric oxide synthase (iNOS) expression and NO production, and thereby enhanced the proliferation and cytotoxic activity of cocultured lymphocytes and macrophages during IL-2 stimulation which we earlier established as an in vitro model of IL-2-induced NO synthesis. Curcumin also decreased apoptosis of cocultured lymphocytes and macrophages during IL-2 stimulation. In contrast, the curcumin-induced changes in proliferation and apoptosis were not observed in cultures of lymphocytes alone, macrophages alone, and cocultured lymphocytes/iNOS-knock out macrophages, all of which produced little nitrite during IL-2 stimulation. In conjunction with IL-2 treatment, oral curcumin administration significantly inhibited IL-2 therapy-induced urinary nitrite/nitrate excretion and iNOS expression of tumor tissues, and further increased the IL-2 therapy-induced prolongation of survival in a murine Meth-A ascites tumor model. Curcumin may be useful as an adjunct to increase the antitumor activity of IL-2 therapy.
authors.affiliation: Departments of *Internal Medicine, Chonbuk National University Medical School, Chonbuk, Korea.
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Song
authors.forename: Joo-Yun
authors.initials: JY
authors.lastname: Yim
authors.forename: Jun-Mo
authors.initials: JM
authors.lastname: Yim
authors.forename: In-Jeong
authors.initials: IJ
authors.lastname: Kang
authors.forename: Hye-Won
authors.initials: HW
authors.lastname: Rho
authors.forename: Hee Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Ho-Young
authors.initials: HY
authors.lastname: Yhim
authors.forename: Na-Ri
authors.initials: NR
authors.lastname: Lee
authors.forename: Eun-Kee
authors.initials: EK
authors.lastname: Song
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Kwak
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Sohn
authors.forename: Chang-Yeol
authors.initials: CY
authors.lastname: Yim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D003474:Curcumin / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2; D016328:NF-kappa B; D009573:Nitrites; D009569:Nitric Oxide; D003474:Curcumin