Multidrug reverting activity toward leukemia cells in a group of new verapamil analogues with low cardiovascular activity

Biscardi, Monica; Teodori, Elisabetta; Caporale, Roberto; Budriesi, Roberta; Balestri, Francesca; Scappini, Barbara; Gavazzi, S.; Grossi, Alberto

doi:10.1016/j.leukres.2005.06.005

Cited by 18 publications

(13 citation statements)

References 26 publications

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“…4D, the effect of naringenin on the mRNA expression of MDR1, MRP1 and MRP2 in all four cell lines was not observed, and similar result was found for verapamil treatment. Previous studies have shown that verapamil can prevent the drug pump of Pgp by inhibiting its activity (32,33). Our results suggest that naringenin enhances the cellular accumulation of doxorubicin through modulating the function of MRPs but not their expression levels.…”

Section: Naringenin Has No Effect On Expression Of Mdr1 and Mrpsmentioning

confidence: 49%

Naringenin Enhances the Anti-Tumor Effect of Doxorubicin Through Selectively Inhibiting the Activity of Multidrug Resistance-Associated Proteins but not P-glycoprotein

Zhang

et al. 2008

Pharm Res

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Section: Naringenin Has No Effect On Expression Of Mdr1 and Mrpsmentioning

confidence: 49%

Naringenin Enhances the Anti-Tumor Effect of Doxorubicin Through Selectively Inhibiting the Activity of Multidrug Resistance-Associated Proteins but not P-glycoprotein

Zhang

et al. 2008

Pharm Res

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“…Despite advances made over the last 30 years, most acute leukaemia remains difficult to cure owing to the development of multidrug resistance (MDR) (Abd El-Ghaffar et al, 2006;Biscardi et al, 2006). The most well-characterised MDR gene product in relapsed acute leukaemia is P-glycoprotein (Pgp) encoded by MDR1 gene (Abd El-Ghaffar et al, 2006).…”

mentioning

confidence: 99%

Anti-Cripto Mab inhibit tumour growth and overcome MDR in a human leukaemia MDR cell line by inhibition of Akt and activation of JNK/SAPK and bad death pathways

Yang

et al. 2007

Br J Cancer

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Doxorubicin (DOX) selection of CCRF-CEM leukaemia cell line resulted in multidrug resistance (MDR) CEM/A7R cell line, which overexpresses MDR, 1 coded P-glycoprotein (Pgp). Here, we report for the first time that oncoprotein Cripto, a founding member of epidermal growth factor-Cripto-FRL, 1-Criptic family is overexpressed in the CEM/A7R cells, and anti-Cripto monoclonal antibodies (Mab) inhibited CEM/A7R cell growth both in vitro and in an established xenograft tumour in severe combined immunodeficiency mice. Cripto Mab synergistically enhanced sensitivity of the MDR cells to Pgp substrates epirubicin (EPI), daunorubicin (DAU) and non-Pgp substrates nucleoside analogue cytosine arabinoside (AraC). In particular, the combination of anti-Cripto Mab at less than 50% of inhibition concentrations with noncytotoxic concentrations of EPI or DAU inhibited more than 90% of CEM/A7R cell growth. Cripto Mab slightly inhibited Pgp expression, and had little effect on Pgp function, indicating that a mechanism independent of Pgp was involved in overcoming MDR. We demonstrated that anti-Cripto Mab-induced CEM/A7R cell apoptosis, which was associated with an enhanced activity of the c-Jun N-terminal kinase/stress-activated protein kinase and inhibition of Akt phosphorylation, resulting in an activation of mitochondrial apoptosis pathway as evidenced by dephosphorylation of Bad at Ser136, Bcl-2 at Ser70 and a cleaved caspase-9.

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“…The different expression of Pgp was crucial in regulating the doxorubicin accumulation in MM98 cells. To correlate the doxorubicin resistance with the induction of Pgp in the present experimental model, the intracellular accumulation and the cytotoxic effect of the drug were measured after a 24-h incubation with dexrazoxane, crocidolite or hypoxia, alone or together with FeNTA, in the presence of 50 mM verapamil, a well-known Pgp inhibitor [27]. Preliminary dose-dependence experiments showed that 50 mM verapamil was the minimal dose able to significantly increase intracellular doxorubicin versus the respective control (data not shown).…”

Section: Activation Of Hif-1a Increased Pgp Expression and Doxorubicimentioning

confidence: 99%

Asbestos induces doxorubicin resistance in MM98 mesothelioma cells via HIF-1

Riganti

Doublier²,

Aldieri³

et al. 2008

European Respiratory Journal

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Human malignant mesothelioma (HMM), which is strongly related to asbestos exposure, exhibits high resistance to many anticancer drugs. Asbestos fibre deposition in the lung may cause hypoxia and iron chelation at the fibre surface. Hypoxia-inducible factor (HIF)-1a, which is upregulated by a decreased availability of oxygen and iron, controls the expression of membrane transporters, such as P-glycoprotein (Pgp), which actively extrude the anticancer drugs. The present study aimed to assess whether asbestos may play a role in the induction of doxorubicin resistance in HMM cells through the activation of HIF-1a and an increased expression of Pgp.After 24-h incubation with crocidolite asbestos or with the iron chelator dexrazoxane, or under hypoxia, HMM cells were tested for HIF-1a activation, Pgp expression, accumulation of doxorubicin and sensitivity to its toxic effect.Crocidolite, dexrazoxane and hypoxia caused HIF-1a activation, Pgp overexpression and increased resistance to doxorubicin accumulation and toxicity. These effects were prevented by the co-incubation with the cell-permeating iron salt ferric nitrilotriacetate, which caused an increase of intracellular iron bioavailability, measured as increased activity of the iron regulatory protein-1.Crocidolite, dexrazoxane and hypoxia induce doxorubicin resistance in human malignant mesothelioma cells by increasing hypoxia-inducible factor-1a activity, through an iron-sensitive mechanism.

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Multidrug reverting activity toward leukemia cells in a group of new verapamil analogues with low cardiovascular activity

Cited by 18 publications

References 26 publications

Naringenin Enhances the Anti-Tumor Effect of Doxorubicin Through Selectively Inhibiting the Activity of Multidrug Resistance-Associated Proteins but not P-glycoprotein

Naringenin Enhances the Anti-Tumor Effect of Doxorubicin Through Selectively Inhibiting the Activity of Multidrug Resistance-Associated Proteins but not P-glycoprotein

Anti-Cripto Mab inhibit tumour growth and overcome MDR in a human leukaemia MDR cell line by inhibition of Akt and activation of JNK/SAPK and bad death pathways

Asbestos induces doxorubicin resistance in MM98 mesothelioma cells via HIF-1

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