Metabolism of ATP-binding cassette drug transporter inhibitors: complicating factor for multidrug resistance

Cnubben, N.H.P.; Wortelboer, Heleen M.; Zanden, Jelmer J. van; Rietjens, Ivonne M. C. M.; Bladeren, P.J. van

doi:10.1517/17425255.1.2.219

Cited by 16 publications

(9 citation statements)

References 128 publications

(56 reference statements)

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“…Flavonoid analogs of Desmosdumotin B have been reported with >100-fold selectivity towards KB-V1 cells (Figure 3) [83,84], though flavonoids are known to have wide-ranging biological activity and selectivity needs to be demonstrated [85]. There is great potential for the screening and discovery of new CS agents against MDR cells, including those expressing other transporters.…”

Section: Discussionmentioning

confidence: 99%

Is resistance useless? Multidrug resistance and collateral sensitivity

Hall

Handley

Gottesman

2009

Trends in Pharmacological Sciences

234

187

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When cancer cells develop resistance to chemotherapeutics, it is frequently conferred by the ATPdependent efflux pump P-glycoprotein (MDR1, P-gp, ABCB1). P-gp can efflux a wide range of cancer drugs; thus its expression confers cross-resistance, termed multidrug resistance (MDR), to a wide range of drugs. Strategies to overcome this resistance have been actively sought for over 30 years, yet no clinical solutions exist. A less understood aspect of MDR is the hypersensitivity of resistant cancer cells to other drugs, a phenomenon generally known as collateral sensitivity (CS). This review highlights the extent of this effect for the first time, discusses hypotheses such as ROS generation to account for the underlying generality of this phenomenon, and proposes the exploitation of CS as a strategy to improve response to chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Is resistance useless? Multidrug resistance and collateral sensitivity

Hall

Handley

Gottesman

2009

Trends in Pharmacological Sciences

234

187

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“…After screening several classes of molecules, we focused on substituted quinolines based on their relative binding constants and bioactivities. Quinolines are known for their antimalarial [Wiesner et al, 2003], antibacterial [Veyssier and Bryskier, 2005], and anticancer [Boyle and Travers, 2006;Cnubben et al, 2005;Kawase and Motohashi, 2003;Levitt and Koty, 1999] activities. Recently, quinolines were examined in ATP-binding cassette drug transporter inhibition [Cnubben et al, 2005], targeting tumor hypoxia [Boyle and Travers, 2006], modulation of multidrug resistance [Kawase and Motohashi, 2003], and tyrosine kinase inhibition [Levitt and Koty, 1999].…”

Section: Discussionmentioning

confidence: 99%

Antitumor effect of substituted quinolines in breast cancer cells

Gakhar

Ohira

Shi

et al. 2008

Drug Development Research

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Cancer is caused in part by the disruption in cell homeostasis, affecting the ability to respond to extracellular signals, triggering some intracellular events that affect gap junctional intercellular communication (GJIC). Cancer cells have reduced or altered GJIC capacity. One feasible approach to reduce growth of cancer cells is to enhance/alter the GJIC. The capability of cells to communicate through the gap junction is negatively related to their growth activity. A computational docking study showed that a new class of substituted quinolines designated as PQs had a relatively high binding to gap junction protein, connexin 43. Thus, PQs were used in this study to assess their effect on human breast cancer cells. Scrape load/dye transfer and colony growth assays were performed to measure GJIC and determine the effect of the PQ compounds on colony formation in human normal mammary epithelial cells (HMEC) and breast cancer cells, respectively. PQs had a significant antitumor effect in human breast cancer cells compared with control without treatment or normal mammary epithelial cells. PQ1 (200 nM) showed a 30% increase in the GJIC in T47D cells; however, there was no effect of PQ treatment on GJIC in normal mammary epithelial cells. In addition to an increase in GJIC, 80-95% growth attenuation was observed by PQ1 in colony growth assay. Moreover, an increase in caspase 3 with PQ-treated cells was observed, suggesting a possible involvement in apoptosis. PQ1-treated animals showed a significant decrease in xenograft tumor growth of T47D cells in nude mice compared with control or tamoxifen-treated animals. The results show that PQ1 has a promising role in exerting antitumor activity in human breast cancer cells. Treatment with PQ1 in T47D cells caused an increase in GJIC activity and active caspase 3, and a decrease in colony growth and cell viability. Drug Dev Res 69 : 526-534,

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“…Some of these agents are listed in Table 5 and any dramatic improvement in the performance of these agents has yet to be reported. The metabolism of some of these inhibitors may limit their effectiveness in cancer therapy [52].…”

Section: The Atp Binding Cassette (Abc) Transportersmentioning

confidence: 99%

The Development of Targeted Therapies for Hepatocellular Cancer

Chattopadhyay¹,

Manas²,

Reeves³

2007

CPD

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Present treatment options for hepatocellular cancer (HCC) are limited to those individuals with good liver function and early stage disease. Unfortunately this includes only a minority of patients, few of which are actually cured of their cancer. Over the last 15-20 years biotechnology has made a very significant impact on medical research, to the extent that we know very much more about the regulation of normal cell growth and death, as well as the mechanisms underlying its disruption in disease processes. This knowledge has and is being rapidly exploited by academic and pharmaceutical organisations, often in collaboration. The result is the development, testing and steady introduction of therapies that target specific abnormalities in cancer cells. Although the safety and effectiveness of the majority of these agents has yet to be established in cirrhotic patients with HCC, we are hopeful that we will shortly see an increase in effective treatment options available for clinical use this disease. This review focuses on aberrant cancer proteins and pathways relevant to HCC, as well as the novel therapies or strategies targeting them, that are currently in the development or testing stages.

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Metabolism of ATP-binding cassette drug transporter inhibitors: complicating factor for multidrug resistance

Cited by 16 publications

References 128 publications

Is resistance useless? Multidrug resistance and collateral sensitivity

Is resistance useless? Multidrug resistance and collateral sensitivity

Antitumor effect of substituted quinolines in breast cancer cells

The Development of Targeted Therapies for Hepatocellular Cancer

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