Ruthenium Complexes Induce HepG2 Human Hepatocellular Carcinoma Cell Apoptosis and Inhibit Cell Migration and Invasion through Regulation of the Nrf2 Pathway

Author： Lu Yiyu   Shen Ting   Yang Hua   Gu Weiguang  

Publisher： MDPI

E-ISSN： 1422-0067|17|5|775-775

ISSN： 1422-0067

Source： International Journal of Molecular Sciences, Vol.17, Iss.5, 2016-05, pp. : 775-775

Access to resources Favorite

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

Ruthenium (Ru) complexes are currently the focus of substantial interest because of their potential application as chemotherapeutic agents with broad anticancer activities. This study investigated the in vitro and in vivo anticancer activities and mechanisms of two Ru complexes—2,3,7,8,12,13,17,18-Octaethyl-21H,23H-porphine Ru(II) carbonyl (Ru1) and 5,10,15,20-Tetraphenyl-21H,23H-porphine Ru(II) carbonyl (Ru2)—against human hepatocellular carcinoma (HCC) cells. These Ru complexes effectively inhibited the cellular growth of three human hepatocellular carcinoma (HCC) cells, with IC50 values ranging from 2.7–7.3 μM. In contrast, the complexes exhibited lower toxicity towards L02 human liver normal cells with IC50 values of 20.4 and 24.8 μM, respectively. Moreover, Ru2 significantly inhibited HepG2 cell migration and invasion, and these effects were dose-dependent. The mechanistic studies demonstrated that Ru2 induced HCC cell apoptosis, as evidenced by DNA fragmentation and nuclear condensation, which was predominately triggered via caspase family member activation. Furthermore, HCC cell treatment significantly decreased the expression levels of Nrf2 and its downstream effectors, NAD(P)H: quinone oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO1). Ru2 also exhibited potent in vivo anticancer efficacy in a tumor-bearing nude mouse model, as demonstrated by a time- and dose-dependent inhibition on tumor growth. The results demonstrate the therapeutic potential of Ru complexes against HCC via Nrf2 pathway regulation.

Related content

Anticancer Effects of Bufalin on Human Hepatocellular Carcinoma HepG2 Cells: Roles of Apoptosis and Autophagy

By Miao Qing   Bi Lin-Lin   Li Xin   Miao Shan   Zhang Jin   Zhang Song   Yang Qian   Xie Yan-Hua   Zhang Jian   Wang Si-Wang  

International Journal of Molecular Sciences, Vol. 14, Iss. 1, 2013-01 ,pp. : 1370-1382 (13)

MDPI

Access to resources Recommend Favorite

Sinulariolide Suppresses Human Hepatocellular Carcinoma Cell Migration and Invasion by Inhibiting Matrix Metalloproteinase-2/-9 through MAPKs and PI3K/Akt Signaling Pathways

By Wu Yu-Jen   Neoh Choo-Aun   Tsao Chia-Yu   Su Jui-Hsin   Li Hsing-Hui  

International Journal of Molecular Sciences, Vol. 16, Iss. 7, 2015-07 ,pp. : 16469-16482 (14)

MDPI

Access to resources Recommend Favorite

Antisense Oligonucleotide Against Clusterin Regulates Human Hepatocellular Carcinoma Invasion Through Transcriptional Regulation of Matrix Metalloproteinase-2 and E-Cadherin

By Chen Dong   Wang Yan   Zhang Kejun   Jiao Xuelong   Yan Bomin   Liang Jun  

International Journal of Molecular Sciences, Vol. 13, Iss. 8, 2012-08 ,pp. : 10594-10607 (14)

MDPI

Access to resources Recommend Favorite

A Homogeneous Polysaccharide from Fructus Schisandra chinensis (Turz.) Baill Induces Mitochondrial Apoptosis through the Hsp90/AKT Signalling Pathway in HepG2 Cells

By Chen Yonglin   Shi Songshan   Wang Huijun   Li Ning   Su Juan   Chou Guixin   Wang Shunchun  

International Journal of Molecular Sciences, Vol. 17, Iss. 7, 2016-06 ,pp. : 1015-1015 (1)

MDPI

Access to resources Recommend Favorite

Transcriptional Activation of Stress Genes and Cytotoxicity in Human Liver Carcinoma (HepG2) Cells Exposed to Pentachlo-rophenol

By Dorsey Waneene C.   Tchounwou Paul B.   Ishaque Ali B.   Shen Elaine  

International Journal of Molecular Sciences, Vol. 3, Iss. 9, 2002-09 ,pp. : 992-1007 (16)

MDPI

Access to resources Recommend Favorite