Anti-tumour activity in non-small cell lung cancer models and toxicity profiles for novel ruthenium(II) based organo-metallic compounds

Guichard, Sylvie; Else, R. W.; Reid, Eilidh M.; Zeitlin, Benjamin David; Aird, Rhona; Muir, Morwenna; Dodds, Michael; Fiebig, H.H.; Sadler, Peter J.; Jodrell, Duncan I.

doi:10.1016/j.bcp.2005.10.053

Cited by 75 publications

(63 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Sp1 is also involved in the nicotine-induced growth of lung cancer cells (Sun et al, 2009). Although the Sp1 inhibitor mithramycin A (MMA), which inhibits the binding of Sp1 to GC-rich sequences in gene promoters, including the Sp1 gene, has an antitumor effect, its cytotoxicity in normal tissues is very high (Guichard et al, 2006;Yang et al, 2010;Tian et al, 2011). Because the down-regulation of Sp1 is an effective therapeutic strategy in antitumorigenesis, it would be worthwhile to develop or discover new cancer therapy drugs that target Sp1 with less cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Betulinic Acid Decreases Specificity Protein 1 (Sp1) Level via Increasing the Sumoylation of Sp1 to Inhibit Lung Cancer Growth

et al. 2012

View full text Add to dashboard Cite

Previous studies have shown that the inhibitory effect of betulinic acid (BA) on specificity protein 1 (Sp1) expression is involved in the prevention of cancer progression, but the mechanism of this effect remains to be delineated. In this study, we determined that BA treatment in HeLa cells increased the sumoylation of Sp1 by inhibiting sentrin-specific protease 1 expression. The subsequent recruitment of E3 ubiquitin-protein ligase RING finger protein 4 resulted in ubiquitin-mediated degradation in a 26S-proteosome-dependent pathway. In addition, both BA treatment and mithramycin A (MMA) treatment inhibited lung tumor growth and down-regulated Sp1 protein expression in Kras G12D -induced lung cancers of bitransgenic mice. In gene expression profiles of Kras G12D -induced lung cancers in bitransgenic mice with and without Sp1 inhibition, 542 genes were affected by MMA treatment. One of the gene products, cyclin A2, which was involved in the S and G 2 /M phase transition during cell cycle progression, was investigated in detail because its expression was regulated by Sp1. The down-regulation of cyclin A2 by BA treatment resulted in decreased retinoblastoma protein phosphorylation and cell cycle G 2 /M arrest. The BA-mediated cellular Sp1 degradation and antitumor effect were also confirmed in a xenograft mouse model by using H1299 cells. The knockdown of Sp1 in lung cancer cells attenuated the tumor-suppressive effect of BA. Taken together, the results of this study clarify the mechanism of BA-mediated Sp1 degradation and identify a pivotal role for Sp1 in the BA-induced repression of lung cancer growth.

show abstract

Section: Introductionmentioning

confidence: 99%

Betulinic Acid Decreases Specificity Protein 1 (Sp1) Level via Increasing the Sumoylation of Sp1 to Inhibit Lung Cancer Growth

et al. 2012

View full text Add to dashboard Cite

show abstract

“…6 The introduction of XY = azopyridine, a strong π-acceptor, as the N,N-chelating ligand has a remarkable effect on the reactivity, especially when Z = 8 We have now investigated the activity of this complex in vivo versus HCT116 human colon cancer xenografts and the distribution of osmium in plasma and tissues. Further insight into the mechanism of action of 1 was obtained from studies of its redox potential, its ability to 4 generate Reactive Oxygen Species (ROS) in cells, and the ability of L-buthioninesulfoximine (L-BSO), a specific inhibitor of γ-glutamyl-cysteine synthetase known to reduce intracellular thiol levels, 9 to enhance the cytotoxicity of the complex.…”

mentioning

confidence: 99%

Anti-colorectal cancer activity of an organometallic osmium arene azopyridine complex

Shnyder

Habtemariam

et al. 2011

Med. Chem. Commun.

View full text Add to dashboard Cite

“…Recently [92], [( 6 -bip)Ru(en)Cl] + has been evaluated in a 13-cell line panel. Particular sensitivity (ca.…”

Section: Metal Arene Complexesmentioning

confidence: 99%

Using coordination chemistry to design new medicines

Ronconi

Sadler

2007

Coordination Chemistry Reviews

568

301

View full text Add to dashboard Cite

Anti-tumour activity in non-small cell lung cancer models and toxicity profiles for novel ruthenium(II) based organo-metallic compounds

Cited by 75 publications

References 22 publications

Betulinic Acid Decreases Specificity Protein 1 (Sp1) Level via Increasing the Sumoylation of Sp1 to Inhibit Lung Cancer Growth

Betulinic Acid Decreases Specificity Protein 1 (Sp1) Level via Increasing the Sumoylation of Sp1 to Inhibit Lung Cancer Growth

Anti-colorectal cancer activity of an organometallic osmium arene azopyridine complex

Using coordination chemistry to design new medicines

Contact Info

Product

Resources

About