Targeting Tumor Proteasome with Traditional Chinese Medicine

Yang, Huanjie; Liu, Jinbao; Dou, Q. Ping

doi:10.2174/157016310791162785

Cited by 11 publications

(6 citation statements)

References 68 publications

(86 reference statements)

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“…More importantly, as unfolding of proteins is the basic requirement for the efficient degradation by the proteasome, misfolded polyQ proteins are reduced in their susceptibility to proteasomal degradation [58]. Interestingly, also other natural compounds such as the tender root of lei gong teng derived from traditional Chinese medicine approaches have been studied concerning potential effects on the activity of the cellular proteasome [59, 60]. …”

Section: Discussionmentioning

confidence: 99%

The Ginkgo biloba Extract EGb 761 Modulates Proteasome Activity and Polyglutamine Protein Aggregation

Stark

Behl

2014

Evidence-Based Complementary and Alternative Medicine

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The standardized Ginkgo biloba extract EGb 761 has well-described antioxidative activities and effects on different cytoprotective signaling pathways. Consequently, a potential use of EGb 761 in neurodegenerative diseases has been proposed. A common characteristic feature of a variety of such disorders is the pathologic formation of protein aggregates, suggesting a crucial role for protein homeostasis. In this study, we show that EGb 761 increased the catalytic activity of the proteasome and enhanced protein degradation in cultured cells. We further investigated this effect in a cellular model of Huntington's disease (HD) by employing cells expressing pathologic variants of a polyglutamine protein (polyQ protein). We show that EGb 761 affected these cells by (i) increasing proteasome activity and (ii) inducing a more efficient degradation of aggregation-prone proteins. These results demonstrate a novel activity of EGb 761 on protein aggregates by enhancing proteasomal protein degradation, suggesting a therapeutic use in neurodegenerative disorders with a disturbed protein homeostasis.

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Section: Discussionmentioning

confidence: 99%

The Ginkgo biloba Extract EGb 761 Modulates Proteasome Activity and Polyglutamine Protein Aggregation

Stark

Behl

2014

Evidence-Based Complementary and Alternative Medicine

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“…For example, the proteasome is inhibited by the thiazole antibiotics thiostrepton and siomycin A, which block the translocation step of protein synthesis in bacteria by binding to the large ribosomal subunits (Pandit et al, 2011). Proteasomes are also reported to be inhibited by green-tea polyphenols (Nam et al, 2001), certain triterpenoids (Tiedemann et al, 2009), and many other electrophilic natural products (see Yang et al, 2010, for review). These compounds induce apoptosis in proliferating cells, but whether apoptosis is due to proteasome inhibition is not clear as these compounds may have dozens if not hundreds of other cellular targets (Liby et al, 2007; Yang et al, 2009).…”

Section: Major Structural Classes Of Inhibitors Of Proteolytic Sites mentioning

confidence: 99%

Proteasome Inhibitors: An Expanding Army Attacking a Unique Target

Kisselev

Linden

Overkleeft

2012

Chemistry & Biology

484

482

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Proteasomes are large, multisubunit proteolytic complexes presenting multiple targets for therapeutic intervention. The 26S proteasome consists of a 20S proteolytic core and one or two 19S regulatory particles. The 20S core contains three types of active sites. Many structurally diverse inhibitors of these active sites, both natural product and synthetic, have been discovered in the last two decades. One, bortezomib, is used clinically for treatment of multiple myeloma, mantle cell lymphoma, and acute allograft rejection. Five more recently developed proteasome inhibitors are in trials for treatment of myeloma and other cancers. Proteasome inhibitors also have activity in animal models of autoimmune and inflammatory diseases, reperfusion injury, promote bone and hair growth, and can potentially be used as anti-infectives. In addition, inhibitors of ATPases and deubiquitinases of 19S regulatory particles have been discovered in the last decade.

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“…The recent approval of bortezomib, a synthetic proteasome inhibitor, for the treatment of relapsed multiple myeloma has paved the way for the discovery of drugs targeting the proteasome, ubiquitinating and deubiquitinating enzymes and of novel ways to administer them [46]. To date, various synthetic and natural products have been reported to inhibit the components of the ubiquitin-proteasome system [46], including traditional Chinese medicines [47]. The new proteasome inhibitors that are now under development include peptide boronic acid analogs MLN9708 and CEP-18770, peptide epoxyketones carfilzomib and PR-047, and NPI-0052, alactone compound [48].…”

Section: Glycyrrhetinic Acid Derivatives As Proteasome Inhibitors: Samentioning

confidence: 99%

Structure-Activity Relationship Analyses of Glycyrrhetinic Acid Derivatives as Anticancer Agents

Lallemand¹,

Gelbcke²,

Dubois³

et al. 2011

MRMC

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Cancer cell resistance to kinase inhibitors and targeted agents, acquisition of a multidrug-resistant (MDR) phenotype and/or intrinsic resistance to apoptosis prevent effective treatment in about 50% of solid cancers in adults, and the percentage is even higher in children. Glycyrrhetinic acid (GA) and some of its derivatives may offer hope in combating cancer types associated with poor prognoses. Some GA derivatives are indeed able to target both the proteasome and peroxisome proliferator-activated receptors (PPARs), two proteins that play major roles in cancer cell biology but are not related to MDR and/or apoptosis-related resistance phenotypes.

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Targeting Tumor Proteasome with Traditional Chinese Medicine

Cited by 11 publications

References 68 publications

The Ginkgo biloba Extract EGb 761 Modulates Proteasome Activity and Polyglutamine Protein Aggregation

The Ginkgo biloba Extract EGb 761 Modulates Proteasome Activity and Polyglutamine Protein Aggregation

Proteasome Inhibitors: An Expanding Army Attacking a Unique Target

Structure-Activity Relationship Analyses of Glycyrrhetinic Acid Derivatives as Anticancer Agents

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