title: Water-Soluble Dinitrosyl Iron Complex (DNIC): a Nitric Oxide Vehicle Triggering Cancer Cell Death via Apoptosis.
abstract: Nitric oxide (NO) is an important cellular signaling molecule that modulates various physiological activities. Angiogenesis-promoting activities of NO-donor drugs have been explored in both experimental and clinical studies. In this study, a structurally well characterized and water-soluble neutral {Fe(NO)2}(9) DNIC [(S(CH2)2OH)(S(CH2)2NH3)Fe(NO)2] (DNIC 2) was synthesized to serve as a NO-donor species. The antitumor activity of DNIC 2 was determined by MTT assay, confocal imaging, and Annexin-V/PI staining. The IC50 values of DNIC 2 were 18.8, 42.9, and 38.6 μM for PC-3, SKBR-3, and CRL5866 tumor cells, respectively. Moreover, DNIC 2 promoted apoptotic cell death via activation of apoptosis-associated proteins and inhibition of survival associated proteins. In particular, DNIC 2 treatment suppressed PC-3 tumor growth by 2.34- and 19.3-fold at 7 and 21 days, in comparison with the control group. These results indicate that water-soluble DNIC 2 may serve as a promising drug for cancer therapy.
authors: Department of Chemistry and Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University , Hsinchu 30013, Taiwan.
authors: Shou-Cheng
authors: SC
authors: Wu
authors: Department of Chemistry and Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University , Hsinchu 30013, Taiwan.
authors: Chung-Yen
authors: CY
authors: Lu
authors: Department of Chemistry and Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University , Hsinchu 30013, Taiwan.
authors: Yi-Lin
authors: YL
authors: Chen
authors: Department of Chemistry and Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University , Hsinchu 30013, Taiwan.
authors: Feng-Chun
authors: FC
authors: Lo
authors: Department of Chemistry and Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University , Hsinchu 30013, Taiwan.
authors: Ting-Yin
authors: TY
authors: Wang
authors: Department of Biological Science and Technology, Institute of Molecular Medicine and Bioengineering, National Chiao Tung University , Hsinchu 30013, Taiwan.
authors: Yu-Jen
authors: YJ
authors: Chen
authors: Translational Research Center, Department of Medical Research, and Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University , Kaohsiung 807, Taiwan.
authors: Shyng-Shiou
authors: SS
authors: Yuan
authors: Department of Chemistry and Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University , Hsinchu 30013, Taiwan.
authors: Wen-Feng
authors: WF
authors: Liaw
authors: Department of Biological Science and Technology, Institute of Molecular Medicine and Bioengineering, National Chiao Tung University , Hsinchu 30013, Taiwan.|Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University , Kaohsiung 807, Taiwan.
authors: Yun-Ming
authors: YM
authors: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007501:Iron / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020030:Nitric Oxide Donors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D009589:Nitrogen Oxides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D014867:Water; C073661:dinitrosyl iron complex; D007501:Iron