Modulation of cisplatin sensitivity in human ovarian carcinoma A2780 and SKOV3 cell lines by sulforaphane

Hunáková, Ľuba; Gronesova, Paulina; Horváthová, Eva; Chalupa, Ivan; Cholujová, Dana; Duraj, J; Sedlák, J

doi:10.1016/j.toxlet.2014.08.018

Cited by 32 publications

(40 citation statements)

References 24 publications

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“…As shown in our experiments, CDDP can arrest both sensitive A2780 as well as resistant A2780/CP cells in G2/M phase of cell cycle what is in line with findings of several reports published on various human ovarian carcinoma cells [31][32][33][34]. This CDDP-induced G2/M phase arrest was accompanied by increased level of DNA damage manifested as the reduced migration of DNA into the tails of comets observed by us in the present investigation, by Hunakova et al [11] as well as by Pfuhler and Wolf [12].…”

Section: Discussionsupporting

confidence: 93%

“…This CDDP‐induced G2/M phase arrest was accompanied by increased level of DNA damage manifested as the reduced migration of DNA into the tails of comets observed by us in the present investigation, by Hunakova et al . as well as by Pfuhler and Wolf .…”

Section: Discussionmentioning

confidence: 82%

“…For the DNA-protectivity assessment (against H 2 O 2 ) in HepG2 cells, the method of SCGE according to Horvathova et al [9] was precisely followed. To study and distinguish frank DNA breaks and DNA damage induced in A2780 and A2780/CP cells with DNAcross-linking agent CDDP, the incubation of the cells with styrene oxide (StO) was carried out as described by Fikrova et al [10] and Hunakova et al [11].…”

Section: Methodsmentioning

confidence: 99%

“…The percentage of DNA in the tail was used as a parameter for the measurement of DNA damage. In experiments for detection of cross-links, the values for the DNA damage are given as percentages of StO-induced DNA migration calculated by the formula suggested by Pfuhler and Wolf [12] and modified by Hunakova et al [11].…”

Section: Methodsmentioning

confidence: 99%

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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: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 82%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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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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“…Of particular interest were results that AGF94 and AGF154 inhibited proliferation of EOC cells with differences in cisplatin sensitivities (Table 1). Thus, IGROV1 (24) and A2780 (41) are generally considered cisplatin sensitive, whereas SKOV3 (41) and TOV112D (42) are cisplatin resistant.…”

Section: Resultsmentioning

confidence: 99%

Dual Targeting of Epithelial Ovarian Cancer Via Folate Receptor α and the Proton-Coupled Folate Transporter with 6-Substituted Pyrrolo[2,3-d]pyrimidine Antifolates

Hou

Gattoc

O’Connor

et al. 2017

Molecular Cancer Therapeutics

128

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Folate uptake in epithelial ovarian cancer (EOC) involves the reduced folate carrier (RFC) and the proton-coupled folate transporter (PCFT), both facilitative transporters, and folate receptor (FR) α. Whereas in primary EOC specimens, FRα is widely expressed and increases with tumor stage, PCFT was expressed independent of tumor stage (by real-time RT-PCR and immunohistochemistry). EOC cell line models, including cisplatin sensitive (IGROV1 and A2780) and resistant (SKOV3 and TOV112D) cells, expressed a 17-fold range of FRα and similar amounts (within ∼2-fold) of PCFT. Novel 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolates AGF94 and AGF154 exhibited potent anti-proliferative activities toward all of the EOC cell lines, reflecting selective cellular uptake by FRα and/or PCFT over RFC. When IGROV1 cells were pretreated with AGF94 at pH 6.8, clonogenicity was potently inhibited, confirming cell killing. FRα was knocked down in IGROV1 cells with lentiviral shRNAs. Two FRα knockdown clones (KD-4 and KD-10) showed markedly reduced binding and uptake of [3H]folic acid and [3H]AGF154 by FRα, but maintained high levels of [3H]AGF154 uptake by PCFT compared to non-targeted control cells. In proliferation assays, KD-4 and KD-10 cells preserved in vitro inhibition by AGF94 and AGF154, compared to a non-targeted control, attributable to residual FRα- and substantial PCFT-mediated uptake. KD-10 tumor xenografts in severe-compromised immune deficient mice were likewise sensitive to AGF94. Collectively, our results demonstrate the substantial therapeutic potential of novel 6-substituted pyrrolo[2,3-d]pyrimidine antifolates with dual targeting of PCFT and FRα toward EOCs that express a range of FRα, along with PCFT, as well as cisplatin resistance.

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Modulation of Myb‐induced NF‐kB ‐STAT3 signaling and resulting cisplatin resistance in ovarian cancer by dietary factors

Tian

Qiao

et al. 2019

Journal Cellular Physiology

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c-Myb regulates tumorigenesis in multiple cancers. Here we show, for the first time, the mechanism of c-Myb-mediated proliferation, invasion, and drug resistance in ovarian cancer (OC), the most lethal gynecological cancer, and a comparative analyses of dietary agents, curcumin, epigallocatechin-3-gallate (EGCG), and sulforaphane in inhibiting c-Myb activity. We evaluated myb expression in patients with OC and found its increased expression in patients with cancer, compared with normal controls and in higher grade tumors, compared with low-grade tumors. Using ES2 and OVCAR3 cell line models, along with the silencing or overexpression of c-Myb, we establish a role of c-Myb in determining resistance to cisplatin. c-Myb overexpression activated NF-κB and STAT3 signaling leading to enhanced proliferation, invasion, and cisplatin resistance. Contrary to this, silencing of c-Myb inhibited proliferation, invasion, and sensitized OC cells to cisplatin. Further, among the dietary agents tested, EGCG almost completely inhibited the c-Myb-induced proliferation and invasion whereas sulforaphane also had significant inhibitory effect. Both compounds significantly sensitized OC cells to cisplatin, reversing the c-Myb effects. Higher c-Myb levels in patients with ovarian cancer lead to poor survival and our results indicate a possible effect of dietary factors EGCG and sulforaphane against c-Mybmediated ovarian cancer progression and chemoresistance.

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Modulation of cisplatin sensitivity in human ovarian carcinoma A2780 and SKOV3 cell lines by sulforaphane

Cited by 32 publications

References 24 publications

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

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

Dual Targeting of Epithelial Ovarian Cancer Via Folate Receptor α and the Proton-Coupled Folate Transporter with 6-Substituted Pyrrolo[2,3-d]pyrimidine Antifolates

Modulation of Myb‐induced NF‐kB ‐STAT3 signaling and resulting cisplatin resistance in ovarian cancer by dietary factors

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