Proteasome is a carrier to translocate doxorubicin from cytoplasm into nucleus

Kiyomiya, Ken-ichi; Matsuo, Sadashige; Kurebe, Masaru

doi:10.1016/s0024-3205(98)00151-9

Cited by 49 publications

(37 citation statements)

References 21 publications

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“…Some studies suggested that anthracyclines bound the proteasome which then acted as a carrier for their entry into cellular nuclei, 28 raising the possibility of an interaction between the 2 drugs. Pharmacodynamic analyses determined if PegLD impacted upon bortezomib-induced proteasome inhibition ( Figure 1).…”

Section: Discussionmentioning

confidence: 99%

Phase 1 trial of the proteasome inhibitor bortezomib and pegylated liposomal doxorubicin in patients with advanced hematologic malignancies

Orłowski

Voorhees

Garcia

et al. 2005

Blood

283

189

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Section: Discussionmentioning

confidence: 99%

Phase 1 trial of the proteasome inhibitor bortezomib and pegylated liposomal doxorubicin in patients with advanced hematologic malignancies

Orłowski

Voorhees

Garcia

et al. 2005

Blood

283

189

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“…Cisplatin inhibits the ubiquitination of proteins, while aclacinomycin A and mitomycin C are not interfering with ubiquitination but inhibit the degradation of ubiquitinated proteins [65,66,67]. Doxorubicin binds to the proteasome without inhibiting it [68]. Vinblastine inhibits proteasome activity in vitro and causes accumulation of ubiquitinated proteins in vivo besides its effect on microtubules [69].…”

Section: Proteasome Inhibitorsmentioning

confidence: 99%

Regulation of apoptosis by the ubiquitin and proteasome pathway

Wójcik

2002

J Cellular Molecular Medi

105

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Regulated proteolysis plays important roles in cell physiology as well as in pathological conditions. In most of the cases, regulated proteolysis is carried out by the ubiquitin-and proteasome-dependent proteolytic system, which is also in charge of the bulk of cytoplasmic proteolysis. However, apoptosis or the process of programmed cell death is regulated by a different proteolytic system, i.e. by caspases, a family of specialized cysteine proteases. Nevertheless, there is plenty of evidence of a crosstalk between the apoptotic pathways and the ubiquitin and proteasome system, whose function in apoptosis appears to be very complex. Proteasome inhibitors induce apoptosis in multiple cell types, while in other they are relatively harmless or even prevent apoptosis induced by other stimuli. Proteasomes degrade specific proteins during apoptosis, but on the other hand some components of the proteasome system are degraded by caspases. The knowledge about the involvement of the ubiquitin-and proteasome-dependent system in apoptosis is already clinically exploited, since proteasome inhibitors are being tested as experimental drugs in the treatment of cancer and other pathological conditions, where manipulation of apoptosis is desirable.

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“…This complex translocates into the nucleus via nuclear pores and dissociates because of drug's higher affinity for DNA than for proteasome. The biochemical consequence of this interaction is the increased targeting of the chemotherapeutic agent at the nucleus compared to the passive diffusion only (24,25). We found PSMB2 downregulated in LoVo-R1 cells compared to LoVo cells, suggesting that this protein may have a role in reducing dox nuclear uptake.…”

Section: Discussionmentioning

confidence: 73%

Identification of proteins associated to multi-drug resistance in LoVo human colon cancer cells

et al. 2009

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Multi-drug resistance (MDR) limits the effectiveness of chemotherapy. P-glycoprotein encoded by the MDR1 gene, is known to be implicated in MDR phenotype, but other factors could be determinant in MDR. The aim of this study was to investigate new molecular factors potentially associated with the MDR phenotype using a proteomic approach. Two dimensional fluorescence difference gel electrophoresis (2D-DIGE) and MALDI-TOF peptide mass fingerprinting were used to determine differentially expressed proteins between LoVo human colon carcinoma cell line and one of its MDR sublines (LoVo-R1). Thirty-four differentially expressed proteins were identified. They were classified into five groups based on their biological functions: i) proteins involved in energy request pathways, ii) in detoxification pathways, iii) in cell survival activity, iv) in drug transport and v) in chaperone functions. Among these proteins, endothelin 1 and proteasome subunit ß2 regulations were validated by immunofluorescence and Western blotting, respectively, showing complete consistency with 2D-DIGE results. In conclusion, the proteomic approach indicates that multiple mechanisms are simultaneously involved in MDR. These might be useful in the search for new forms of interventional therapeutic approaches for MDR reversal. Abbreviations: MDR, multi-drug resistance; 2D-DIGE, two dimensional difference in gel electrophoresis; MALDI-TOF, matrix-assisted laser desorption ionization-time-of-flight; P-gp, P-glycoprotein

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Proteasome is a carrier to translocate doxorubicin from cytoplasm into nucleus

Cited by 49 publications

References 21 publications

Phase 1 trial of the proteasome inhibitor bortezomib and pegylated liposomal doxorubicin in patients with advanced hematologic malignancies

Phase 1 trial of the proteasome inhibitor bortezomib and pegylated liposomal doxorubicin in patients with advanced hematologic malignancies

Regulation of apoptosis by the ubiquitin and proteasome pathway

Identification of proteins associated to multi-drug resistance in LoVo human colon cancer cells

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