Gallium maltolate inhibits human cutaneous T-cell lymphoma tumor development in mice.
Cutaneous T-cell lymphomas (CTCLs) represent a heterogeneous group of non-Hodgkin's lymphoma characterized by an accumulation of malignant CD4 T cells in the skin. The group IIIa metal salt, gallium nitrate, is known to have antineoplastic activity against B-cell lymphoma in humans, but its activity in CTCLs has not been elaborated in detail. Herein, we examined the antineoplastic efficacy of a gallium compound, gallium maltolate (GaM), in vitro and in vivo with murine models of CTCLs. GaM inhibited cell growth and induced apoptosis of cultured CTCL cells. In human CTCL xenograft models, peritumoral injection of GaM limited the growth of CTCL cells, shown by fewer tumor formations, smaller tumor sizes, and decreased neovascularization in tumor microenvironment. To identify key signaling pathways that have a role in GaM-mediated reduction of tumor growth, we analyzed inflammatory cytokines, as well as signal transduction pathways in CTCL cells treated by GaM. IFN-γ-induced chemokines and IL-13 were found to be notably increased in GaM-treated CTCL cells. However, immunosuppressive cytokines, such as IL-10, were decreased with GaM treatment. Interestingly, both oxidative stress and p53 pathways were involved in GaM-induced cytotoxicity. These results warrant further investigation of GaM as a therapeutic agent for CTCLs.
Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin.
Xuesong
X
Wu
Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin.
Timothy W
TW
Wang
Department of Medicine, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin.
George M
GM
Lessmann
Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin.
Jamal
J
Saleh
Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin.
Xiping
X
Liu
Department of Medicine, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin.
Christopher R
CR
Chitambar
Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address: sthwang@mcw.edu.
Sam T
ST
Hwang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D064593:Heterografts; D006801:Humans; D066298:In Vitro Techniques; D016410:Lymphoma, T-Cell, Cutaneous / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D051379:Mice; D009942:Organometallic Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D011753:Pyrones / Q000494:pharmacology / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000098:blood supply / Q000473:pathology* / Q000517:prevention & control*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D016207:Cytokines; D009942:Organometallic Compounds; D011753:Pyrones; D016159:Tumor Suppressor Protein p53; C512662:gallium maltolate