Molecular changes to HeLa cells on continuous exposure to cisplatin or paclitaxel

Takara, Kohji; Obata, Yukihisa; Yoshikawa, Eri; Kitada, Noriaki; Sakaeda, Toshiyuki; Ohnishi, Noriaki; Yokoyama, Teruyoshi

doi:10.1007/s00280-006-0226-5

Cited by 44 publications

(48 citation statements)

References 35 publications

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“…The effects of calcium antagonists on the sensitivity to mitoxantrone in HeLa and HeLa/SN100 cells were evaluated with a WST-1 assay (13)(14)(15). Cells (1x10 3 / well) were seeded onto 96-well plates in 100 µl DMEM without any drugs.…”

Section: Chemicalsmentioning

confidence: 99%

“…HeLa/SN100 cells overexpressed ABCG2/BCRP but not ABCB1/MDR1 (12). This is a useful tool for clarifying the details of the ABCG2/BCRP-mediated resistance mechanism and comparing it with other resistance mechanisms of paclitaxel-resistant (HeLa/TXL) or cisplatin-resistant (HeLa/ CDDP) cells established previously (13).…”

Section: Introductionmentioning

confidence: 99%

“…In the accumulation experiments, HeLa and HeLa/SN100 cells (2x10 5 /well) were seeded onto 24-well plates in 1 ml/well DMEM and incubated for 48 h in a humidified atmosphere containing 5% CO 2 at 37˚C (13,16). After pre-culture, cells were washed twice with warmed HBSS, and then, the accumulation experiments were started with the addition of 1 ml fresh HBSS containing Hoechst33342 (3 µM) or Hoechst33342 (3 µM) plus calcium antagonist (final concentration, 0.1, 1, or 10 µM), and cells were further incubated for specific periods (5, 15, 30, 60, 90, or 120 min) at 37˚C.…”

Section: Hoechst33342 Transport Experimentsmentioning

confidence: 99%

“…Previously, we established various types of resistant cells appropriate for examining the novel mechanism of resistance and techniques for reversing resistance (12,13). One type, HeLa/SN100, was selected from HeLa cells by exposure to an active metabolite of irinotecan hydrochloride, SN-38 (12).…”

Section: Introductionmentioning

confidence: 99%

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Differential effects of calcium antagonists on ABCG2/BCRP-mediated drug resistance and transport in SN-38-resistant HeLa cells

et al. 2011

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Abstract. The effects of 9 calcium antagonists on ABCG2/ BCRP-mediated resistance and transport were examined in HeLa and SN-38-resistant HeLa (HeLa/SN100) cells, overexpressing ABCG2/BCRP. Sensitivity to mitoxantrone, an ABCG2/BCRP substrate, in HeLa/SN100 cells was significantly reversed by the coexistence of the calcium antagonists, except for diltiazem and verapamil. The accelerated transport activity of Hoechst33342, an ABCG2/BCRP substrate, in HeLa/SN100 cells was significantly decreased by the presence of the calcium antagonists, except for diltiazem, nifedipine or verapamil, returning to the level of HeLa cells. The present study classifies the calcium antagonists into 3 categories: strong (benidipine, felodipine, nicardipine, nisoldipine and nitrendipine), moderate (amlodipine and nifedipine) and weak (diltiazem and verapamil) inhibitors of ABCG2/BCRP.

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Section: Chemicalsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Hoechst33342 Transport Experimentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Differential effects of calcium antagonists on ABCG2/BCRP-mediated drug resistance and transport in SN-38-resistant HeLa cells

et al. 2011

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“…These transporters can use the energy of ATP hydrolysis to transport a wide range of substances across cell membranes (Leonard et al, 2003;Takara et al, 2006;Chattopadhyay et al, 2008). The multidrug resistance (MDR) efflux pumps ABC subfamily B member 1 (P-glycoprotein), ABCC1 (MRP1), ABCC2 (MRP2), and ABCG2 (BCRP and MXR) actively expel numerous types of drugs from cancer cells, thereby conferring resistance to those agents (Leslie et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Expression of Aryl Hydrocarbon Receptor Nuclear Translocator Enhances Cisplatin Resistance by Upregulating MDR1 Expression in Cancer Cells

et al. 2013

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The identification of molecular pathways in cancer cells is important for understanding the cells' underlying biology and for designing effective cancer therapies. We demonstrate that the expression of aryl hydrocarbon receptor nuclear translocator (ARNT) is critical during the development of cisplatin resistance. The reduced expression of ARNT was correlated with cisplatininduced cell death in drug-sensitive cells. In addition, suppression of ARNT reversed the characteristics of cisplatin-resistant cells, making these cells cisplatin-sensitive, and significantly enhanced caspase-3 activation, DNA fragmentation, and apoptosis. The inhibition of colony formation, regulated by cisplatin, was more significant in ARNT-knockdown cells than in parental cells. In a xenograft analysis of severe combined immunodeficiency mice, cisplatin also efficiently inhibited ARNT-deficient c4 tumors but not ARNT-containing vT2 tumor formation. Furthermore, the downregulation of multidrug resistance 1 (MDR1) expression and retention of drugs in cells caused by suppression of ARNT, resulting in the resensitization of drug-resistant cells to cisplatin, was observed. When overexpressed, ARNT interacted with Sp1 to enhance the expression of MDR1 through Sp1-binding sites on the MDR1 promoter, resulting in a reversal of the effect of cisplatin on cell death. In addition, ARNT-induced MDR1 expression was inhibited in Sp1-knockdown cells. These results reveal previously unrecognized, multifaceted functions of ARNT in establishing the drug-resistant properties of cancer cells by the upregulation of MDR1, highlighting ARNT's potential as a therapeutic target in an important subset of cancers.

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Fgfr1 and the IIIc isoform of Fgfr2 play critical roles in the metanephric mesenchyme mediating early inductive events in kidney development

Sims‐Lucas

Cusack

Baust

et al. 2010

Developmental Dynamics

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Fibroblast growth factor receptors (Fgfrs) have critical roles in kidney development. FgfrIIIb is thought to act in epithelium, while FgfrIIIc functions in mesenchyme. We aimed to determine roles of Fgfr2IIIc in kidney development. Mice with deletion of Fgfr2IIIc (Fgfr2IIIc−/−) had normal kidneys. Combination of Fgfr2IIIc−/− with conditional deletion of Fgfr1 in metanephric mesenchyme (MM) (Fgfr1Mes−/−Fgfr2IIIc−/−) had small but identifiable MM at E10.5, expressing mesenchymal markers including Eya1, Six2, Pax2 and Gdnf (unlike Fgfr1/2Mes−/− mice that have no obvious MM). E11.5 Fgfr1Mes−/−Fgfr2IIIc−/− mice had rudimentary MM expressing only Eya1. Control, Fgfr2IIIc−/−, and Fgfr1Mes−/−Fgfr2IIIc−/− kidney mesenchymal tissues also express Fgfr2IIIb. In ureteric lineages, E10.5 Fgfr1Mes−/−Fgfr2IIIc−/− embryos had ureteric outgrowth (sometimes multiple buds); however, by E11.5 Gdnf absence lead to no ureteric elongation or branching (similar to Fgfr1/2Mes−/− mice). Beyond E12.5, Fgfr1Mes−/−Fgfr2IIIc−/− mice had no renal tissue. In conclusion, Fgfr2IIIc and Fgfr1 in kidney mesenchyme (together) are critical for normal early renal development.

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Molecular changes to HeLa cells on continuous exposure to cisplatin or paclitaxel

Cited by 44 publications

References 35 publications

Differential effects of calcium antagonists on ABCG2/BCRP-mediated drug resistance and transport in SN-38-resistant HeLa cells

Differential effects of calcium antagonists on ABCG2/BCRP-mediated drug resistance and transport in SN-38-resistant HeLa cells

Expression of Aryl Hydrocarbon Receptor Nuclear Translocator Enhances Cisplatin Resistance by Upregulating MDR1 Expression in Cancer Cells

Fgfr1 and the IIIc isoform of Fgfr2 play critical roles in the metanephric mesenchyme mediating early inductive events in kidney development

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