Reversal of multidrug resistance by the inhibition of ATP-binding cassette pumps employing “Generally Recognized As Safe” (GRAS) nanopharmaceuticals: A review

Sosnik, Alejandro

doi:10.1016/j.addr.2013.09.002

Cited by 92 publications

(48 citation statements)

References 235 publications

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“…In particular the ABC transporter B1, also known as p-glycoprotein or MDR1, transports a broad spectrum of cytostatic drugs, and its high expression was found associated with unfavorable treatment outcome in several clinical chemotherapy trials (33). These findings prompted clinical trials to exploit the inhibition of ABC transporter activity in order to improve cytostatic efficacy (34,35). Such trials have met variable success, due to incomplete inhibitor efficacy as well as the abundance of transporter proteins, of which the human ABC transporter family only comprises more than 46 different proteins (34,36).…”

Section: Discussionmentioning

confidence: 99%

“…These findings prompted clinical trials to exploit the inhibition of ABC transporter activity in order to improve cytostatic efficacy (34,35). Such trials have met variable success, due to incomplete inhibitor efficacy as well as the abundance of transporter proteins, of which the human ABC transporter family only comprises more than 46 different proteins (34,36). Although most drug transporters pump cytostatic drugs as single substrate molecules across the plasma membrane, drugs can also be detoxified by subcellular sequestration and, in consequence, secretory vesicles (13,14).…”

Section: Discussionmentioning

confidence: 99%

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Nuclear Trapping through Inhibition of Exosomal Export by Indomethacin Increases Cytostatic Efficacy of Doxorubicin and Pixantrone

Koch

Aung

Vogel

et al. 2016

Clinical Cancer Research

111

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Purpose: Although R-CHOP-based immunochemotherapy cures significant proportions of patients with aggressive B-cell lymphoma, tumor cell susceptibility to chemotherapy varies, with mostly fatal outcome in cases of resistant disease. We and others have shown before that export of cytostatic drugs contributes to drug resistance. Now we provide a novel approach to overcome exosome-mediated drug resistance in aggressive B-cell lymphomas.Experimental Design: We used well-established centrifugation protocols to purify exosomes from DLBCL cell lines and detected anthracyclines using FACS and HPLC. We used shRNA knockdown of ABCA3 to determine ABCA3 dependence of chemotherapy susceptibility and monitored ABCA3 expression after indomethacin treatment using qPCR. Finally, we established an in vivo assay using a chorioallantoic membrane (CAM) assay to determine the synergy of anthracycline and indomethacin treatment. Results:We show increased efficacy of the anthracycline doxorubicin and the anthracenedione pixantrone by suppression of exosomal drug resistance with indomethacin. B-cell lymphoma cells in vitro efficiently extruded doxorubicin and pixantrone, in part compacted in exosomes. Exosomal biogenesis was critically dependent on the expression of the ATP-transporter A3 (ABCA3). Genetic or chemical depletion of ABCA3 augmented intracellular retention of both drugs and shifted the subcellular drug accumulation to prolonged nuclear retention. Indomethacin increased the cytostatic efficacy of both drugs against DLBCL cell lines in vitro and in vivo in a CAM assay.Conclusions: We propose pretreatment with indomethacin toward enhanced antitumor efficacy of anthracyclines and anthracenediones. Clin Cancer Res; 22(2); 395-404. Ó2015 AACR.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nuclear Trapping through Inhibition of Exosomal Export by Indomethacin Increases Cytostatic Efficacy of Doxorubicin and Pixantrone

Koch

Aung

Vogel

et al. 2016

Clinical Cancer Research

111

View full text Add to dashboard Cite

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“…В табл. 1 представлены сведения относительно участия АВС-транспортеров в лекарственной устойчивости РМЖ [12][13][14][15][16][17][18][19][20], а также перечислены их ингибиторы [16,[21][22][23][24][25][26][27]. Как можно видеть, значительное количество раз-ных транспортных белков влияет на чувствительность клеток РМЖ к широкому кругу лекарственных препа-ратов.…”

Section: механизмы лекарственной устойчивостиunclassified

News in the studies of multidrug resistance of breast cancer cells

Stavrovskaya¹,

Guens²

2015

Usp. mol. onkol

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“…For many mechanisms the cancer cells can be resistant to chemotherapy, but the most important one is the expression of the ATP-binding cassette (ABC) superfamily proteins, which are the largest group of transmembrane proteins. These proteins can protect the cells from the chemotherapy by pumping the drugs out of cells after consuming ATP (Sosnik 2013). Many studies have shown that drug resistance in dogs was also due to the expression of ABC proteins, such as P-glycoprotein (PGP), breast cancer resistance protein (BCRP), multidrug resistance-associated protein 1 (MRP1) and multidrug resistance--associated protein 3 (MRP3) (Nakaichi et al 2007, Honscha et al 2009, Pawlowski et al 2013, Tomiyasu et al 2014.…”

Section: Introductionmentioning

confidence: 99%

Establishment of 5-Fluorouracil-resistant canine mammary tumor cell line

Zhou¹,

Zhang²,

Pei³

et al. 2017

Polish Journal of Veterinary Sciences

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Canine mammary tumors are the most common neoplasms in intact female dogs. The surgery cannot always solve the problem, chemotherapy are recommend to these patients. However, chemotherapy could always fail because of multidrug resistance (MDR). Through stepwise increasing 5-Fluorouracil (5-FU) concentration in the culture medium, a 5-FU-resistant canine mammary tumor cell line CMT7364/5-FU was established to disclose the molecular mechanism of the drug resistance. Cell morphology, cell sensitivity to drugs, growth curves, expression of proteins, and chemo-sensitivity in vivo were compared between the parental cell line and resistant cell line. As compared it to its parental cell line (CMT7364), CMT7364/5-FU showed different morphology, cross-resistant to other chemo-drugs and a prolonged population doubling time (PDT). The drug efflux pump proteins (ABCB1 and ABCG2) in CMT7364/5-FU were up-regulated. In vivo, the similar result revealed that CMT7364/5-FU cell line was more resistant to 5-FU. In conclusion, a 5-FU-resistant canine mammary tumor cell line (CMT7364/5-FU) was successfully established, it can serve as a good model for researching the mechanism of MDR and screening effective agents to reverse drug resistance.

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Reversal of multidrug resistance by the inhibition of ATP-binding cassette pumps employing “Generally Recognized As Safe” (GRAS) nanopharmaceuticals: A review

Cited by 92 publications

References 235 publications

Nuclear Trapping through Inhibition of Exosomal Export by Indomethacin Increases Cytostatic Efficacy of Doxorubicin and Pixantrone

Nuclear Trapping through Inhibition of Exosomal Export by Indomethacin Increases Cytostatic Efficacy of Doxorubicin and Pixantrone

News in the studies of multidrug resistance of breast cancer cells

Establishment of 5-Fluorouracil-resistant canine mammary tumor cell line

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