Water-soluble dinitrosyl iron complex (DNIC): A nitric oxide vehicle triggering cancer cell death via apoptosis

Shou Cheng Wu, Chung Yen Lu, Yi Lin Chen, Feng Chun Lo, Ting Yin Wang, Yu Jen Chen, Shyng Shiou Yuan, Wen Feng Liaw*, Yun-Ming Wang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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(CH 2 ) 2 OH)(S(CH 2 ) 2 NH 3 )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 IC 50 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.

Original languageEnglish
Pages (from-to)9383-9392
Number of pages10
JournalInorganic Chemistry
Volume55
Issue number18
DOIs
StatePublished - 19 Sep 2016

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