New approaches in identifying drugs to inactivate oncogene products

Liu, Ruiwu; Hsieh, Jennifer C.Y.; Lam, Kit S.

doi:10.1016/j.semcancer.2003.11.003

Cited by 19 publications

(8 citation statements)

References 81 publications

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“…In silico screening plays an important role in drug-design [21]. The method used here was developed to identify potential new inhibitors of the CSN-associated kinases, CK2 and PKD.…”

Section: Resultsmentioning

confidence: 99%

“…Simultaneously the cells were stained with PI. By the double staining the test discriminates between intact (FITC - /PI - ), apoptotic (FITC + /PI - ) and necrotic cells (FITC + /PI + ) [21]. First, HeLa cells were incubated with the indicated inhibitors at different concentrations (20 or 50 μM) for 24 h. After harvesting and washing with PBS cells were resuspended in 100 μl annexin V binding buffer (containing 10 mM HEPES/NaOH, pH 7.4, 140 mM NaCl, 2.5 mM CaCl 2 ).…”

Section: Methodsmentioning

confidence: 99%

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Novel curcumin- and emodin-related compounds identified by in silico 2D/3D conformer screening induce apoptosis in tumor cells

et al. 2005

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Background: Inhibition of the COP9 signalosome (CSN) associated kinases CK2 and PKD by curcumin causes stabilization of the tumor suppressor p53. It has been shown that curcumin induces tumor cell death and apoptosis. Curcumin and emodin block the CSN-directed c-Jun signaling pathway, which results in diminished c-Jun steady state levels in HeLa cells. The aim of this work was to search for new CSN kinase inhibitors analogue to curcumin and emodin by means of an in silico screening method.

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“…In silico screening plays an important role in drug-design [21]. The method used here was developed to identify potential new inhibitors of the CSN-associated kinases, CK2 and PKD.…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Novel curcumin- and emodin-related compounds identified by in silico 2D/3D conformer screening induce apoptosis in tumor cells

et al. 2005

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“…everal different experimental and in silico approaches have been developed to identify new genes and proteins that could be useful in the diagnosis or treatment of cancer (1)(2)(3). To identify genes that encode membrane or membrane-associated proteins that are present in breast and prostate cancers but have limited expression in normal and essential organs, we developed a molecular approach in which a cDNA library is generated from membrane-associated polyribosomal RNA that encodes membrane and secreted proteins and cytokeratins.…”

mentioning

confidence: 99%

High expression of a cytokeratin-associated protein in many cancers

Egland

Liu²,

Squires³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…Combinatorial chemistry is a powerful technology in simultaneously generating thousands of unique chemical entities [28]. We have generated 10 combinatorial chemical libraries of 9400 unique small molecules.…”

Section: Discussionmentioning

confidence: 99%

LAS0811: From Combinatorial Chemistry to Activation of Antioxidant Response Element

Zhu

Baek

Liu

et al. 2009

BioMed Research International

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The antioxidant response element (ARE) and its transcription factor, nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), are potential targets for cancer chemoprevention. We sought to screen small molecules synthesized with combinatorial chemistry for activation of ARE. By high-throughput screening of 9400 small molecules from 10 combinatorial chemical libraries using HepG2 cells with an ARE-driven reporter, we have identified a novel small molecule, 1,2-dimethoxy-4,5-dinitrobenzene (LAS0811), as an activator of the ARE. LAS0811 upregulated the activity of NAD(P)H:quinone oxidoreductase 1 (NQO1), a representative antioxidative enzyme regulated by ARE. It enhanced production of an endogenous reducing agent, glutathione (GSH). In addition, LAS0811 induced expression of heme oxygenase 1 (HO1), which is an ARE-regulated enzyme with anti-inflammatory activity. Furthermore, LAS0811 reduced cell death due to the cytotoxic stress of a strong oxidant, t-butyl hydroperoxide (t-BOOH). Mechanistically, LAS0811 upregulated the expression of Nrf2 and promoted its translocation into the nuclei leading to subsequent ARE activation. Taken together, LAS0811 is a novel activator of the ARE and its associated detoxifying genes and, thus, a potential agent for cancer chemoprevention.

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New approaches in identifying drugs to inactivate oncogene products

Cited by 19 publications

References 81 publications

Novel curcumin- and emodin-related compounds identified by in silico 2D/3D conformer screening induce apoptosis in tumor cells

Novel curcumin- and emodin-related compounds identified by in silico 2D/3D conformer screening induce apoptosis in tumor cells

High expression of a cytokeratin-associated protein in many cancers

LAS0811: From Combinatorial Chemistry to Activation of Antioxidant Response Element

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