Administration of isothiocyanate (E-4IB) and cisplatin leads to altered signalling and lysosomal export in human ovarian carcinoma sensitive- and cisplatin-resistant cells

Duraj, J; Hunáková, Ľuba; Bodo, Juraj; Jakubíková, Jana; Chovancová, Jana; Sedlák, J

doi:10.4149/neo_2009_03_208

Cited by 7 publications

(7 citation statements)

References 43 publications

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“…Bcl‐2 – another Bcl‐2 gene family protein – represents the founding member of cell death inhibiting oncoproteins. We did not recognize any substantial changes in Bcl‐2 expression in both sensitive A2780 and resistant A2780/CP cells; however, there is a slight increase in basal level of Bcl‐2 in resistant cells observed by our team in the past . Apoptotic stimulation induces cleavage of caspase 9 to p35 or p37 kDa subunits.…”

Section: Resultsmentioning

confidence: 57%

Salidroside, a Chemopreventive Glycoside, Diminishes Cytotoxic Effect of Cisplatin in Vitro

Zdurienčíková

Cholujová

Duraj

et al. 2017

Basic Clin Pharma Tox

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Natural products represent the source or the inspiration for the majority of the active ingredients of medicines because of their structural diversity and a wide range of biological effects. Our aims in this study were (i) to synthesize enzymatically salidroside (SAL), the most effective phenylethanoid glycoside in Rhodiola species; (ii) to examine its antioxidant capacity using cell-free assays (reducing power, DPPH radicals scavenging and Fe -chelating assays); (iii) to assess its DNA-protective potential on plasmid DNA (DNA topology assay) and in HepG2 cells (comet assay) damaged by Fe ions and hydrogen peroxide, respectively; and (iv) to investigate the effects of SAL, cisplatin (CDDP) and combined treatments of SAL + CDDP on cell viability (MTT test), level of DNA damage (comet assay), proliferation, cell cycle (flow cytometry) and the expression of signalling molecules associated with cell growth and apoptotic pathways (Western immunoblotting). We found out that SAL manifested low antioxidant and DNA-protective capacity in all assays used. In both parental A2780 and CDDP-resistant A2780/CP human ovarian carcinoma cells, SAL itself exerted in fact no impact on the viability, while in combination with CDDP it showed antagonistic effect supporting the chemopreventive activity on the CDDP-induced cell damage. These results were confirmed by the partial reversal of the cell cycle alterations and the DNA damage level, as well as with partial restoration of cell survival/signalling pathways, when the expression of these molecules partially returned to their proper levels.

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Section: Resultsmentioning

confidence: 57%

Salidroside, a Chemopreventive Glycoside, Diminishes Cytotoxic Effect of Cisplatin in Vitro

Zdurienčíková

Cholujová

Duraj

et al. 2017

Basic Clin Pharma Tox

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“…Activation of NF-κB contributes to aggressive tumor growth and also to chemotherapy resistance, and, on the other hand, NF-κB inactivation mediates decreased activity of anti-apoptotic-and increased upregulation of apoptotic genes [27,28]. In line with this fact, in recent years much effort has been invested in developing NF-κB-blocking agents, including CDDP, natural compounds and their semisynthetic or synthetic analogues [29][30][31].…”

Section: Discussionmentioning

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

neo

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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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“…This compound provoked activation of ERK 1/2, c-Jun N terminal kinase and p38 signaling pathways [56] in leukemia cell line (HL-60). When this compound was [57].…”

Section: Isothiocyanatesmentioning

confidence: 96%

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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Administration of isothiocyanate (E-4IB) and cisplatin leads to altered signalling and lysosomal export in human ovarian carcinoma sensitive- and cisplatin-resistant cells

Cited by 7 publications

References 43 publications

Salidroside, a Chemopreventive Glycoside, Diminishes Cytotoxic Effect of Cisplatin in Vitro

Salidroside, a Chemopreventive Glycoside, Diminishes Cytotoxic Effect of Cisplatin in Vitro

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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