Gallium maltolate inhibits human cutaneous T-cell lymphoma tumor development in mice

Xuesong Wu, Timothy W. Wang, George M. Lessmann, Jamal Saleh, Xiping Liu, Christopher R. Chitambar, Samuel T Hwang

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)877-884
Number of pages8
JournalJournal of Investigative Dermatology
Volume135
Issue number3
DOIs
StatePublished - Mar 12 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Gallium maltolate inhibits human cutaneous T-cell lymphoma tumor development in mice'. Together they form a unique fingerprint.

Cite this