Imatinib resistance in multidrug-resistant K562 human leukemic cells

Assef, Yanina Andrea; Rubio, Fernanda; Colò, G.; Mónaco, Silvana del; Costas, Mónica Alejandra; Kotsias, Basilio A.

doi:10.1016/j.leukres.2008.09.024

Cited by 40 publications

(26 citation statements)

References 49 publications

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“…Although the debate about the clinical relevance of efflux-mediated drug resistance is currently ongoing, HCT-15 and COLO320DM cells express MDR1 and are resistant to several chemotherapy drugs (18)(19)(20). A number of chemotherapy-resistant cell lines have been developed using K562 leukemia cells (21)(22)(23). In this study, we also produced adriamycin-resistant K562 cells and confirmed that these cells overexpressed MDR1 and were resistant to paclitaxel.…”

Section: Discussionsupporting

confidence: 62%

TAK-960, a Novel, Orally Available, Selective Inhibitor of Polo-Like Kinase 1, Shows Broad-spectrum Preclinical Antitumor Activity in Multiple Dosing Regimens

Hikichi

Honda

Hikami

et al. 2012

Molecular Cancer Therapeutics

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Polo-like kinase 1 (PLK1) is a serine/threonine protein kinase involved in key processes during mitosis. Human PLK1 has been shown to be overexpressed in various human cancers, and elevated levels of PLK1 have been associated with poor prognosis, making it an attractive target for anticancer therapy. 7,8,is a novel, investigational, orally bioavailable, potent, and selective PLK1 inhibitor that has shown activity in several tumor cell lines, including those that express multidrug-resistant protein 1 (MDR1). Consistent with PLK1 inhibition, TAK-960 treatment caused accumulation of G 2 -M cells, aberrant polo mitosis morphology, and increased phosphorylation of histone H3 (pHH3) in vitro and in vivo. TAK-960 inhibited proliferation of multiple cancer cell lines, with mean EC 50 values ranging from 8.4 to 46.9 nmol/L, but not in nondividing normal cells (EC 50 >1,000 nmol/L). The mutation status of TP53 or KRAS and MDR1 expression did not correlate with the potency of TAK-960 in the cell lines tested. In animal models, oral administration of TAK-960 increased pHH3 in a dose-dependent manner and significantly inhibited the growth of HT-29 colorectal cancer xenografts. Treatment with once daily TAK-960 exhibited significant efficacy against multiple tumor xenografts, including an adriamycin/paclitaxel-resistant xenograft model and a disseminated leukemia model. TAK-960 has entered clinical evaluation in patients with advanced cancers. Mol Cancer Ther; 11(3); 700-9. Ó2011 AACR.

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Section: Discussionsupporting

confidence: 62%

TAK-960, a Novel, Orally Available, Selective Inhibitor of Polo-Like Kinase 1, Shows Broad-spectrum Preclinical Antitumor Activity in Multiple Dosing Regimens

Hikichi

Honda

Hikami

et al. 2012

Molecular Cancer Therapeutics

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“…Furthermore, several molecular pathways, such as NF-κB, ERK/MAPK, and p38-MAPK, among others, are also associated with the regulation of Pgp expression in cancer cells (47)(48)(49). A recent study showed that the MDR phenotype in K562 cells could be reversed by inhibition of the NF-κB pathway, suggesting a regulation of Pgp through modulation of NF-κB (50). NF-κB activation also contributes to survivin expression, and likewise NF-κB inhibition downregulates survivin (51,52).…”

Section: Discussionmentioning

confidence: 99%

P-glycoprotein and survivin simultaneously regulate vincristine-induced apoptosis in chronic myeloid leukemia cells

Souza

Vasconcelos²,

Reis³

et al. 2011

Int J Oncol

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Abstract. Overexpression of P-glycoprotein (Pgp/ABCB1) in tumor cells is associated with a classic phenotype of multidrug resistance (MDR). Moreover, some members of the inhibitor of apoptosis protein (IAP) family, such as survivin, contribute to an apoptosis-resistant phenotype, by inhibiting chemotherapyinduced cell death and promoting MDR. By using Western blotting, qRT-PCR, Annexin V and immunofluorescence assays we have demonstrated a relationship between Pgp and survivin in a prior sensitive chronic myeloid leukemia (CML) cell line (K562). A high dose of vincristine induced a concomitant overexpression of Pgp and survivin, which was associated with a low apoptotic index in the K562 cell line. In addition, we observed a cytoplasmic co-localization of Pgp and survivin, suggesting a functional association between these two proteins in apoptosis control by a common mechanism. In summary, our data suggest that Pgp and survivin should be analyzed in aggregate because they may have significant impact on drug resistance in CML cells.

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“…Quinacrine Sensitizes RKO and HT29 Cells to TRAIL-and L-OHP-induced Cell Death-Constitutive NF-B activation has conferred resistance to TRAIL (61,62) and to various chemotherapeutic agents including L-OHP in cancer cells (33,(63)(64)(65). HT29 and RKO cells, resistant to TRAIL-mediated apoptosis, were selected to elucidate whether inhibition of NF-B signaling by quinacrine could potentiate TRAIL-induced apoptosis in these cell lines.…”

Section: Journal Of Biological Chemistry 19165mentioning

confidence: 99%

Inhibition of NF-κB Signaling by Quinacrine Is Cytotoxic to Human Colon Carcinoma Cell Lines and Is Synergistic in Combination with Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) or Oxaliplatin

Jani

DeVecchio

Mazumdar

et al. 2010

Journal of Biological Chemistry

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Imatinib resistance in multidrug-resistant K562 human leukemic cells

Cited by 40 publications

References 49 publications

TAK-960, a Novel, Orally Available, Selective Inhibitor of Polo-Like Kinase 1, Shows Broad-spectrum Preclinical Antitumor Activity in Multiple Dosing Regimens

TAK-960, a Novel, Orally Available, Selective Inhibitor of Polo-Like Kinase 1, Shows Broad-spectrum Preclinical Antitumor Activity in Multiple Dosing Regimens

P-glycoprotein and survivin simultaneously regulate vincristine-induced apoptosis in chronic myeloid leukemia cells

Inhibition of NF-κB Signaling by Quinacrine Is Cytotoxic to Human Colon Carcinoma Cell Lines and Is Synergistic in Combination with Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) or Oxaliplatin

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