FK506 confers chemosensitivity to anticancer drugs in glioblastoma multiforme cells by decreasing the expression of the multiple resistance-associated protein-1

Garrido, Wallys; Munoz, Marcia A.; Martin, R. H.; Quezada, Claudia

doi:10.1016/j.bbrc.2011.06.087

Cited by 25 publications

(29 citation statements)

References 35 publications

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“…Recent studies showed that temozolomide, the first choice of chemotherapy drug for GBM treatment induces ROS production (21) and that resistance to this drug involved mitochondria dysfunction and a decrease in ROS production (24). Other studies showing that inhibition of MRP1 activity or expression (25)(26)(27) lead to an increase in the response of GBM cell lines to chemotherapeutic drugs indicating the importance of this protein in GBM drug resistance. Combination of citral and antineoplastic drugs does not seem to sensitize GBM cells as the resulting decrease in cell viability is equivalent to the added effect of both drugs (Figure 7).…”

Section: Discussionmentioning

confidence: 96%

Apoptosis-Inducing Effects ofMelissa officinalisL. Essential Oil in Glioblastoma Multiforme Cells

Queiroz

Takiya

Guimarães

et al. 2014

Cancer Investigation

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Current therapies for glioblastoma multiforme (GBM) are not effective. This study investigated the activity of the M. officinalis essential oil (EO) and its major component (citral) in GBM cell lines. Both EO and citral decreased the viability and induced apoptosis of GBM cells as demonstrated by DNA fragmentation and caspase-3 activation. Antioxidant prevented citral-induced death, indicating its dependence on the production of reactive oxygen species. Citral downmodulated the activity and inhibited the expression of multidrug resistance associated protein 1 (MRP1). These results show that EO, through its major component, citral, may be of potential interest for the treatment of GBM.

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Section: Discussionmentioning

confidence: 96%

Apoptosis-Inducing Effects ofMelissa officinalisL. Essential Oil in Glioblastoma Multiforme Cells

Queiroz

Takiya

Guimarães

et al. 2014

Cancer Investigation

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“…It has been reported that MRP1-transfected HEK293 cells showed increased resistance to etoposide compared with the parental cells (Nunoya et al, 2003). Furthermore, T98G glioblastoma cells treated with tacrolimus, which decreases MRP1 expression, were reported to show increased sensitivity to etoposide (Garrido et al, 2011). These previous studies suggested the involvement of MRP1 in etoposide resistance but did not determine the intracellular amount of etoposide.…”

Section: Discussionmentioning

confidence: 97%

“…MRP1 has been reported to transport various anticancer drugs, such as vincristine, doxorubicin, epirubicin, and methotrexate (Zeng et al, 2001;Nunoya et al, 2003;Garrido et al, 2011), and it was detected in three out of six stomach cancer cell lines, but in only one out of five breast cancer cell lines. Among the stomach cancer cell lines, a .16.2-fold difference was observed in the expression level of MRP1, which was the second-largest difference after that of glucose transporter GLUT1 expression (19.3-fold difference) ( Table 1).…”

Section: Protein Expression Levels Of Membrane Proteins Inmentioning

confidence: 99%

Identification of Transporters Associated with Etoposide Sensitivity of Stomach Cancer Cell Lines and Methotrexate Sensitivity of Breast Cancer Cell Lines by Quantitative Targeted Absolute Proteomics

Obuchi

Ohtsuki²,

Uchida

et al. 2012

Mol Pharmacol

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Membrane transporter proteins may influence the sensitivity of cancer cells to anticancer drugs that can be recognized as substrates. The purpose of this study was to identify proteins that play a key role in the drug sensitivity of stomach and breast cancer cell lines by measuring the absolute protein expression levels of multiple transporters and other membrane proteins and examining their correlation to drug sensitivity. Absolute protein expression levels of 90 membrane proteins were examined by quantitative targeted absolute proteomics using liquid chromatography-linked tandem mass spectrometry. Among them, 11 and 14 membrane proteins, including transporters, were present in quantifiable amounts in membrane fraction of stomach cancer and breast cancer cell lines, respectively. In stomach cancer cell lines, the protein expression level of multidrug resistance-associated protein 1 (MRP1) was inversely correlated with etoposide sensitivity. MK571, an MRP inhibitor, increased both the cell-to-medium ratio of etoposide and the etoposide sensitivity of MRP1-expressing stomach cancer cell lines. In breast cancer cell lines, the protein expression level of reduced folate carrier 1 (RFC1) was directly correlated with methotrexate (MTX) sensitivity. Initial uptake rate and steady-state cell-to-medium ratio of [ 3 H]MTX were correlated with both RFC1 expression level and MTX sensitivity. These results suggest that MRP1 modulates the etoposide sensitivity of stomach cancer cell lines and RFC1 modulates the MTX sensitivity of breast cancer cell lines. Our results indicate that absolute quantification of multiple membrane proteins could be a useful strategy for identification of candidate proteins involved in drug sensitivity.

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“…Finally, a renewed interest in targeting drug resistance mechanisms has recently emerged (39,40), this being especially relevant in STS, where only a few active drugs are available (41)(42)(43). Thus, blocking MRP1 expression by nilotinib resulted in intracellular doxorubicin retention, reverting MDR activity and showing synergistic antiproliferative effects in in vitro analysis (44).…”

Section: Discussionmentioning

confidence: 99%

MRP1 Overexpression Determines Poor Prognosis in Prospectively Treated Patients with Localized High-Risk Soft Tissue Sarcoma of Limbs and Trunk Wall: An ISG/GEIS Study

Martin‐Broto

Gutiérrez

Ramos

et al. 2014

Molecular Cancer Therapeutics

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Patients with localized high-risk soft tissue sarcomas (STS) of the limbs and trunk wall still have a considerable metastatic recurrence rate of more than 50%, in spite of adjuvant chemotherapy. This drugceiling effect of chemotherapy in sarcoma setting could be explained, at least partially, by multidrug resistance (MDR) mechanisms. The aim of this study was to ascertain whether mRNA and protein expression of ABCB1 (P-glycoprotein), ABCC1 (MRP1), and GSTA1 (glutathione S-transferase pi) was prognostic in localized high-risk STS. Immunohistochemistry and reverse transcriptase-PCR studies were performed from biopsies at the time of diagnosis. Patients of this series were prospectively enrolled into a phase III trial that compared three versus five cycles of epirubicin plus ifosfamide. The series of 102 patients found 41 events of recurrence and 37 of death with a median follow-up of 68 months. In univariate analysis, variables with a statistically significant relationship with relapse-free survival (RFS) were: MRP1 expression (5-year RFS rate of 23% in positive cases and 63% in negative cases, P ¼ 0.029), histology (5-year RFS rate of 74% in undifferentiated pleomorphic sarcoma and 43% in synovial sarcoma, P ¼ 0.028), and ABCC1 expression (5-year RFS rate of 33% in overexpression and 65% in downregulation, P ¼ 0.012). Combined ABCC1/MRP1 was the only independent prognostic factor for both RFS (HR ¼ 2.704, P ¼ 0.005) and overall survival (HR ¼ 2.208, P ¼ 0.029). ABCC1/MRP1 expression shows robust prognostic relevance in patients with localized high-risk STS treated with anthracycline-based chemotherapy, which is the standard front line treatment in STS. This finding deserves attention as it points to a new targetable protein in STS.

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FK506 confers chemosensitivity to anticancer drugs in glioblastoma multiforme cells by decreasing the expression of the multiple resistance-associated protein-1

Cited by 25 publications

References 35 publications

Apoptosis-Inducing Effects ofMelissa officinalisL. Essential Oil in Glioblastoma Multiforme Cells

Apoptosis-Inducing Effects ofMelissa officinalisL. Essential Oil in Glioblastoma Multiforme Cells

Identification of Transporters Associated with Etoposide Sensitivity of Stomach Cancer Cell Lines and Methotrexate Sensitivity of Breast Cancer Cell Lines by Quantitative Targeted Absolute Proteomics

MRP1 Overexpression Determines Poor Prognosis in Prospectively Treated Patients with Localized High-Risk Soft Tissue Sarcoma of Limbs and Trunk Wall: An ISG/GEIS Study

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