The iron chelator, Dp44mT, effectively inhibits human oral squamous cell carcinoma cell growth in vitro and in vivo

Jehn Chuan Lee, Kun Chun Chiang, Tsui Hsia Feng, Yu Jen Chen, Sung Ting Chuang, Ke Hung Tsui, Li Chuan Chung, Horng Heng Juang

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

Oral squamous cell carcinoma (OSCC) is a common malignancy with a growing worldwide incidence and prevalence. The N-myc downstream regulated gene (NDRG) family of NDRG1, 2, 3, and mammary serine protease inhibitor (Maspin) gene are well-known modulators in the neoplasia process. Current research has considered iron chelators as new anti-cancer agents; however, the anticancer activities of iron chelators and their target genes in OSCC have not been well investigated. We showed that iron chelators (Dp44mT, desferrioxamine (DFO), and deferasirox) all significantly inhibit SAS cell growth. Flow cytometry further indicated that Dp44mT inhibition of SAS cells growth was partly due to induction of G1 cell cycle arrest. Iron chelators enhanced expressions of NDRG1 and NDRG3 while repressing cyclin D1 expression in OSCC cells. The in vivo antitumor effect on OSCC and safety of Dp44mT were further confirmed through a xenograft animal model. The Dp44mT treatment also increased Maspin protein levels in SAS and OECM-1 cells. NDRG3 knockdown enhanced the growth of OECM-1 cells in vitro and in vivo. Our results indicated that NDRG3 is a tumor suppressor gene in OSCC cells, and Dp44mT could be a promising therapeutic agent for OSCC treatment.

Original languageEnglish
Article number1435
JournalInternational journal of molecular sciences
Volume17
Issue number9
DOIs
Publication statusPublished - Sep 2016
Externally publishedYes

Keywords

  • Deferasirox
  • DFO
  • Maspin
  • NDRG1
  • NDRG3

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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