Int. J. Mol. Sci. 2016, 17(9), 1435; https://doi.org/10.3390/ijms17091435
The Iron Chelator, Dp44mT, Effectively Inhibits Human Oral Squamous Cell Carcinoma Cell Growth in Vitro and in Vivo
Jehn-Chuan Lee 1,2,†, Kun-Chun Chiang 3,†, Tsui-Hsia Feng 4, Yu-Jen Chen 5, Sung-Ting Chuang 6
, Ke-Hung Tsui 7, Li-Chuan Chung 8,*
and Horng-Heng Juang 6,7,*
, Ke-Hung Tsui 7, Li-Chuan Chung 8,*
and Horng-Heng Juang 6,7,*
1
Department of Otolaryngology, Mackay Memorial Hospital, Taipei 105, Taiwan
2
School of Medicine, Mackay Medical College, New Taipei City 207, Taiwan
3
Zebrafish Center, Department of General Surgery, Chang Gung Memorial Hospital and University, Keelung 204, Taiwan
4
School of Nursing, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan
5
Department of Radiation On Cology, Mackay Memorial Hospital, Taipei 105, Taiwan
6
Department of Anatomy, College of Medicine, Chang Gung University, 259 Wen-Hua 1st Road, Kwei-Shan, Tao-Yuan 333, Taiwan
7
Department of Urology, Chang Gung Memorial Hospital-Linkou, Kwei-Shan, Tao-Yuan 244, Taiwan
8
Department of General Education Center, Mackay Medicine, Nursing and Management College, New Taipei City 207, Taiwan
*
Authors to whom correspondence should be addressed.
Academic Editors: Sotiris Hadjikakou and Nick Hadjiliadis
Received: 16 July 2016 / Revised: 16 July 2016 / Accepted: 24 August 2016 / Published: 31 August 2016
(This article belongs to the Special Issue Recent Advances in Metal Based Drugs)
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. View Full-TextKeywords:
NDRG1; NDRG3; Maspin; DFO; deferasirox
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Lee, J.-C.; Chiang, K.-C.; Feng, T.-H.; Chen, Y.-J.; Chuang, S.-T.; Tsui, K.-H.; Chung, L.-C.; Juang, H.-H. The Iron Chelator, Dp44mT, Effectively Inhibits Human Oral Squamous Cell Carcinoma Cell Growth in Vitro and in Vivo. Int. J. Mol. Sci. 2016, 17, 1435.
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