Title: Water-Soluble Dinitrosyl Iron Complex (DNIC): a Nitric Oxide Vehicle Triggering Cancer Cell Death via Apoptosis
Authors: Wu, Shou-Cheng
Lu, Chung-Yen
Chen, Yi-Lin
Lo, Feng-Chun
Wang, Ting-Yin
Chen, Yu-Jen
Yuan, Shyng-Shiou
Liaw, Wen-Feng
Wang, Yun-Ming
Department of Biological Science and Technology
Issue Date: 19-Sep-2016
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)(2)OH)(S(CH2)(2)NH3)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 mu M for PC-3, SKBR-3, and CRLS866 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.
URI: http://dx.doi.org/10.1021/acs.inorgchem.6b01562
ISSN: 0020-1669
DOI: 10.1021/acs.inorgchem.6b01562
Volume: 55
Issue: 18
Begin Page: 9383
End Page: 9392
Appears in Collections:Articles