Syrbactin class proteasome inhibitor-induced apoptosis and autophagy occurs in association with p53 accumulation and Akt/PKB activation in neuroblastoma

Archer, Crystal R.; Koomoa, Dana Lynn T.; Mitsunaga, Erin M.; Clerc, Jérôme; Shimizu, Mariko; Kaiser, Markus; Schellenberg, Barbara; Dudler, Robert; Bachmann, André S.

doi:10.1016/j.bcp.2010.03.031

Cited by 42 publications

(49 citation statements)

References 34 publications

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“…Also, inhibition of autophagic degradation can often lead to the accumulation of LC3-II proteins [94]; however, in all the above-cited papers rapidly activated autophagy after proteasome inhibition was observed [75,85]. The presence of a considerably increased number of autophagosomes at various stages was postulated as the most convincing proof of active ongoing autophagy after proteasome inhibition by different groups of proteasome inhibitors [24,88,91,[95][96][97].…”

Section: Direct Effects Of Proteasome Inhibition On Autophagy Markersmentioning

confidence: 99%

Crosstalk between autophagy and proteasome protein degradation systems: possible implications for cancer therapy

Wójcik

2014

Folia Histochem Cytobiol.

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Abstract:The Ubiquitin-Proteasomes System (UPS) and autophagy, two main intracellular protein degradation pathways within the eukaryotic cells which were originally regarded as rather independent, seem to be very closely related. Proteasome inhibitors, including the multipathway inhibitor bortezomib, are drawing increased attention for their therapeutic potential in the treatment of chronic inflammation and cancer, especially tumours with a high degree of malignancy. The over-activation of autophagy induces cell death and may act as a powerful tumour-suppressing mechanism. However, autophagy, serving as an important mechanism to generate nutrients in time of cellular stresses, may directly contribute to the survival of cells treated with proteasome inhibitors, and in consequence, may decrease the effectiveness of therapy. Results of studies performed on several cancer cell lines demonstrated synergy between proteasome inhibitors and autophagy inhibitors. Those results became the base for ongoing clinical trials investigating autophagy inhibition in combination with anti-cancer therapies, including bortezomib. This review provides summary of the latest data on the functioning of the UPS and the mechanisms of autophagy. The new insights describing the main pathways of autophagy activation in response to UPS inhibition related to: (i) Unfolded Protein Response, (ii) PI3K/Akt/mTOR pathway, and (iii) formation of aggresomes, are discussed. It is concluded that concomitant inhibition of the two main cellular protein degradation systems may provide new therapeutic modalities for cancer treatment.

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Section: Direct Effects Of Proteasome Inhibition On Autophagy Markersmentioning

confidence: 99%

Crosstalk between autophagy and proteasome protein degradation systems: possible implications for cancer therapy

Wójcik

2014

Folia Histochem Cytobiol.

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“…We previously found that SylA inhibits cancer cell proliferation (Coleman et al, 2006) and, as a result of a multi-national collaboration, we discovered that SylA inhibits the proteasome (Archer et al, 2010;Groll et al, 2008). Importantly, this study provided the first…”

Section: Introductionmentioning

confidence: 65%

“…Glidobactins (Oka et al, 1988a,b,c,d) and cepafungins Terui et al, 1990) are structurally related molecules, and together, they form a new family of 12-membered lactam proteasome inhibitors, the syrbactins (Figure 1). The total synthesis of syringolin A and syringolin B has been reported by three independent groups (Clerc et al, 2009bDai & Stephenson 2010;Pirrung et al, 2010) and the syrbactins were evaluated in biological systems (Archer et al, 2010;Clerc et al, 2009aClerc et al, ,b, 2010Clerc et al, , 2011Coleman et al, 2006;Groll et al, 2008).…”

Section: Research Articlementioning

confidence: 99%

“…The CellTiter 96 Aqueous One solution Cell Proliferation Assay [2-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt; MTS] (Promega, San Luis Obispo, CA, USA) was performed as previously described (Archer et al, 2010) and used to determine the viability of cancer cells after 24 h treatment with TIR-203 at indicated concentrations (0-10 µM) by measuring the absorbance at 490 nm using the Multi-Mode Synergy™ MX Microplate Reader (BioTek, Inc., Winooski, VT, USA) and data expressed in percent (%) cell survival relative to control (untreated) cells. SylA and bortezomib were used as controls for comparison.…”

Section: Cell Viability Assaymentioning

confidence: 99%

“…The cell culture-based proteasome-Glo inhibition assay was performed as previously described (Archer et al, 2010). Solid white 96-well microtiter cell culture plates were seeded with cells as indicated and treated with TIR-203.…”

Section: Proteasome Inhibition Assaymentioning

confidence: 99%

See 2 more Smart Citations

Syringolin B-inspired proteasome inhibitor analogue TIR-203 exhibits enhanced biological activity in multiple myeloma and neuroblastoma

Opoku-Ansah

Ibarra‐Rivera

Pirrung

et al. 2011

Pharmaceutical Biology

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Total Synthesis of Syringolin A and Improvement of Its Biological Activity

et al. 2014

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The development process for syringolin A analogues having improved proteasome inhibitory and antitumor activity is described. The strategy was to first establish a convergent synthesis of syringolin A using a rare intramolecular Ugi three‐component reaction in the last stage of the synthesis, so as to gain access toa set of structure‐based analogues. The inhibitory activity of chymotrypsin‐like activity of 20S proteasome was largely improved by targeting the S3 subsite of the β5 subunit. Cytotoxic activity was also improved by installing the membrane‐permeable substituent. These biological properties are comparable to those of bortezomib, a clinically used first‐line proteasome inhibitor.

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Syrbactin class proteasome inhibitor-induced apoptosis and autophagy occurs in association with p53 accumulation and Akt/PKB activation in neuroblastoma

Cited by 42 publications

References 34 publications

Crosstalk between autophagy and proteasome protein degradation systems: possible implications for cancer therapy

Crosstalk between autophagy and proteasome protein degradation systems: possible implications for cancer therapy

Syringolin B-inspired proteasome inhibitor analogue TIR-203 exhibits enhanced biological activity in multiple myeloma and neuroblastoma

Total Synthesis of Syringolin A and Improvement of Its Biological Activity

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