Apoptotic effect of ethyl-4-isothiocyanatobutanoate is associated with DNA damage, proteasomal activity and induction of p53 and p21cip1/waf1

Bodo, Juraj; Jakubíková, Jana; Chalupa, Ivan; Bartosova, Zdena; Horáková, K; Floch, L.; Sedlák, J

doi:10.1007/s10495-006-8760-5

Cited by 9 publications

(8 citation statements)

References 51 publications

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“…Cells were harvested at the indicated times and lysed as previously described (Bodo et al 2006). Lysis buffer was added to the solid tumors, and samples were sonicated four times for 10 sec each time with 10 sec intervals on ice to rupture the cells.…”

Section: Western Blot Analysismentioning

confidence: 99%

Quantitative In Situ Detection of Phosphoproteins in Fixed Tissues Using Quantum Dot Technology

Bodo

Durkin

Hsi

2009

J Histochem Cytochem.

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S U M M A R Y Detection and quantitation of phosphoproteins (PPs) in fixed tissues will become increasingly important as additional inhibitors of protein kinases enter clinical use and new disease entities are defined by molecular changes affecting PP levels. We characterize fixation conditions suitable for accurate PP quantitation that are achievable in a clinical laboratory and illustrate the utility of in situ quantitation of PPs by quantum dot (QD) nanocrystals in two models: (1) a therapeutic model demonstrating effects of a targeted therapeutic (quantitative reduction of phospho-GSK3b) in xenografts treated with enzastaurin; and (2) a diagnostic model that identifies elevated levels of nuclear phospho-STAT5 in routine bone marrow biopsies from patients with acute myeloid leukemia based on the presence of the activating FLT3-ITD mutation. Finally, we document production of a wellcharacterized tissue microarray of widely available cell lines as a multilevel calibrator for validating numerous phosphoprotein assays. QD immunofluorescence is an ideal method for in situ quantitation of PPs in fixed samples, providing valuable cell type-specific and subcellular information about pathway activation in primary tissues. (J Histochem Cytochem 57:701-708, 2009)

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Section: Western Blot Analysismentioning

confidence: 99%

Quantitative In Situ Detection of Phosphoproteins in Fixed Tissues Using Quantum Dot Technology

Bodo

Durkin

Hsi

2009

J Histochem Cytochem.

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“…Further, the cells were cooled and incubated on ice for 10 minutes and then PI (50 μg/ml) was added. Finally, the stained cells were analyzed using Beckman FACS Canto II flow cytometer [22]. Cell cycle was analysed with MultiCycle AV Plug-in to FCS Express version 3 software, Los Angeles, CA, USA.…”

Section: Methodsmentioning

confidence: 99%

Proteasome inhibition leads to altered signaling in the proteome of cisplatin-resistant human ovarian carcinoma cell line

Duraj¹,

Pastorek²,

Vitkovska³

et al. 2014

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To address a precise view into molecular mechanisms of apoptotic signaling pathways after single-or combinatory treatments with specific NF-κB-or proteasome inhibitors and/or cisplatin (CDDP), flow cytometry and western blotting of the cell proteome in human ovarian chemosensitive-and CDDP-resistant cell lines were used. We report here that proteasome inhibition (but not NF-κB inhibition) caused marked alterations in the cell proliferation and cell cycle, as well as in the levels of signaling anti-and pro-apoptotic proteins PARP, NF-κB, IκB-α, Bcl-2, Bax, and lysosome-associated LAMP-1 and ATP-7B molecules in particular proteome fractions. These findings refer to the possibility of regulation of CDDP resistance, inclusive the capacity of lysosomes to export CDDP in certain human ovarian cancer cells by proteasome inhibition.

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“…Among the synthetic isothiocyanates, ethyl-4-isothiocyanatobutanoate (E-41B) (Fig. 5) plays a relevant role in this area [55]. This compound provoked activation of ERK 1/2, c-Jun N terminal kinase and p38 signaling pathways [56] in leukemia cell line (HL-60).…”

Section: Isothiocyanatesmentioning

confidence: 99%

Kinase Regulation by Sulfur and Selenium Containing Compounds

Sanmartín

Plano²,

Font³

et al. 2011

CCDT

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Kinases are enzymes that are involved in a wide-range of cellular targets such as cell proliferation, metabolism, survival and apoptosis. Aberrations in the activity of the kinases have been linked to many human diseases such as diabetes, inflammation and cancer. The discovery of more than 518 kinases encoded by the human genome has spurred the development of rapid screening techniques for potential drugs against these enzymes and these have been identified as interesting targets for medicinal chemistry programs, especially in cancer therapy. On the other hand, sulfur and selenium have been increasingly recognized as essential elements in biology and medicine. Converging data from epidemiological and clinical studies have highlighted these elements as effective chemopreventive agents, particularly against various types of cancer (prostate, lung, breast, leukemia, colon, skin, lymphome, thyroid, pancreas, liver). These elements act through a wide range of potential mechanisms where one identified signal pathway event is kinase modulation, which is common for the two elements and emerges as a valid target. The kinases modulated by sulfur and selenium derivatives include MAP, ERK, JNK, Akt, Cdc2, Cyclin B1 and Cdc25c amongst others. Although both of the elements in question are in the same group in the periodic table and have similar biochemistries, there are relevant differences related to redox potentials, stabilities, oxidation states and anticancer activity. Literature data suggest that the replacement of sulfur by selenium in established cancer chemopreventive agents results in more effective chemopreventive analogs. In view of the multi-target kinase mechanisms in preventing cellular transformation, as well as the differences and similarities between them, in this review we focus on the development of new structures that contain selenium and/or sulfur and discuss our understanding of the regulation of antitumoral effects with emphasis on kinase modulation activity and its implications in cancer.

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Apoptotic effect of ethyl-4-isothiocyanatobutanoate is associated with DNA damage, proteasomal activity and induction of p53 and p21cip1/waf1

Cited by 9 publications

References 51 publications

Quantitative In Situ Detection of Phosphoproteins in Fixed Tissues Using Quantum Dot Technology

Quantitative In Situ Detection of Phosphoproteins in Fixed Tissues Using Quantum Dot Technology

Proteasome inhibition leads to altered signaling in the proteome of cisplatin-resistant human ovarian carcinoma cell line

Kinase Regulation by Sulfur and Selenium Containing Compounds

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