Changes in the activity of proteasomes in vivo induced by oxidative stress or para-aminobenzoic acid in loach embryos

Шарова, Н. П.; Stroeva, O. G.; Erokhov, Pavel A.; Dmitrieva, S. B.; Usova, T. A.

doi:10.1134/s1607672907040096

Cited by 3 publications

(3 citation statements)

References 5 publications

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“…MSB is known to induce oxidative stress by the generation of superoxide radicals in the intracellular medium, which damage the tertiary and quaternary structure of proteins including proteasomes [ 19 , 21 ]. A cellular proteasome pool is not homogenous: cells predominantly contain 26S- and 20S-proteasomes with different mechanisms of substrate recognition [ 22 ].…”

Section: Resultsmentioning

confidence: 99%

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Combined Effect of Bortezomib and Menadione Sodium Bisulfite on Proteasomes of Tumor Cells: The Dramatic Decrease of Bortezomib Toxicity in a Preclinical Trial

Astakhova

Morozov

Erokhov

et al. 2018

Cancers

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Tumor growth is associated with elevated proteasome expression and activity. This makes proteasomes a promising target for antitumor drugs. Current antitumor drugs such as bortezomib that inhibit proteasome activity have significant side effects. The purpose of the present study was to develop effective low-toxic antitumor compositions with combined effects on proteasomes. For compositions, we used bortezomib in amounts four and ten times lower than its clinical dose, and chose menadione sodium bisulfite (MSB) as the second component. MSB is known to promote oxidation of NADH, generate superoxide radicals, and as a result damage proteasome function in cells that ensure the relevance of MSB use for the composition development. The proteasome pool was investigated by the original native gel electrophoresis method, proteasome chymotrypsin-like activity—by Suc-LLVY-AMC-hydrolysis. For the compositions, we detected 10 and 20 μM MSB doses showing stronger proteasome-suppressing and cytotoxic in cellulo effects on malignant cells than on normal ones. MSB indirectly suppressed 26S-proteasome activity in cellulo, but not in vitro. At the same time, MSB together with bortezomib displayed synergetic action on the activity of all proteasome forms in vitro as well as synergetic antitumor effects in cellulo. These findings determine the properties of the developed compositions in vivo: antitumor efficiency, higher (against hepatocellular carcinoma and mammary adenocarcinoma) or comparable to bortezomib (against Lewis lung carcinoma), and drastically reduced toxicity (LD50) relative to bortezomib. Thus, the developed compositions represent a novel generation of bortezomib-based anticancer drugs combining high efficiency, low general toxicity, and a potentially expanded range of target tumors.

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Section: Resultsmentioning

confidence: 99%

“…The second one is menadione sodium bisulfite (MSB) (Vikasolum, vitamin K3). MSB promotes oxidation of NADH, generates superoxide radicals and as a result damages proteasome function in the intracellular medium [ 17 , 18 , 19 ]. Besides, MSB can cause tumor cell death [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Combined Effect of Bortezomib and Menadione Sodium Bisulfite on Proteasomes of Tumor Cells: The Dramatic Decrease of Bortezomib Toxicity in a Preclinical Trial

Astakhova

Morozov

Erokhov

et al. 2018

Cancers

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“…In this connection, patent on siRNA targeting the subunit PSMD10 of the 19S subparticle is important (US20080071075) [90]. Besides, menadione bisulfite was discovered to violate functions of the 19S subparticle [91]. We believe that both these methods related to the destruction of the 19S subparticle functions are very useful in the case of addressed delivery of siRNA and/or menadione bisulfite into tumors.…”

Section: Current and Future Developmentsmentioning

confidence: 98%

Multiple Forms of Proteasomes and their Role in Tumor Fate

Zakharova¹

2008

EMI

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Mammalian and human cells contain multiple forms of proteasomes different in their structure and functions. 26S-proteasome pool regulates most cellular processes through ATP-and ubiquitin-dependent hydrolysis of proteins participating in these processes. This function is possible due to 19S-subparticle capable to recognize ubiquitinated proteins, unfold and direct them into the proteolytic chamber. 20S-proteasome pool is capable to degrade some damaged and foreign proteins in an ATP-and ubiquitin-independent manner. Among both proteasome pools, the immune proteasomes effectively produce antigen epitopes for MHC class I molecules and play a crucial role in the antitumor immunity. Excluding the immune proteasomes from their cells, numerous tumors avoid the immune system. On the contrary, tumor cells enhance the expression of the housekeeping proteasomes and 19S-subparticle.At this time, bortezomib, a patented proteasome inhibitor, is used as an anticancer therapy. This drug induces the cell cycle arrest and apoptosis of dividing tumor cells. However, bortezomib causes, firstly, deviations in immune functions, secondly, the increase of the housekeeping proteasome expression by a feedback mechanism. Taking into account the recent patents, we consider prospects of the development of new drugs directed to the regulation of the expression of the immune and housekeeping proteasomes and 19S-subparticle in tumor cells.

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Growth status of Scots pine artificial stands under the influence of para-aminobenzoic acid

Ivanov

Марченко

Nartov

et al. 2015

Contemp. Probl. Ecol.

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Changes in the activity of proteasomes in vivo induced by oxidative stress or para-aminobenzoic acid in loach embryos

Cited by 3 publications

References 5 publications

Combined Effect of Bortezomib and Menadione Sodium Bisulfite on Proteasomes of Tumor Cells: The Dramatic Decrease of Bortezomib Toxicity in a Preclinical Trial

Combined Effect of Bortezomib and Menadione Sodium Bisulfite on Proteasomes of Tumor Cells: The Dramatic Decrease of Bortezomib Toxicity in a Preclinical Trial

Multiple Forms of Proteasomes and their Role in Tumor Fate

Growth status of Scots pine artificial stands under the influence of para-aminobenzoic acid

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