Inhibitor of polyamine catabolism MDL72.527 restores the sensitivity to doxorubicin of monocytic leukemia Thp-1 cells infected with human cytomegalovirus

Федорова, Н. Е.; Chernoryzh, Yana Yu; Vinogradskaya, G. R.; Emelianova, Svetlana S.; Zavalyshina, Larisa E.; Yurlov, K.I.; Zakirova, Natalia F.; Verbenko, V. N.; Kochetkov, Sergey N.; Кущ, А А; Ivanov, Alexander

doi:10.1016/j.biochi.2018.12.012

Cited by 7 publications

(9 citation statements)

References 48 publications

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“…The antiviral effects of DFMO on various viruses have also been demonstrated ( Masalova et al, 2017 ; Mounce et al, 2016a ; Mounce et al, 2016b ; Tuomi et al, 1980 ), suggesting that DFMO is a potential broad-spectrum antiviral drug. Other polyamine-targeted agents, including DENSpm (an inducer of SAT1), MDL 72757 (an inhibitor of PAOX) and other drugs regulating the hypusination of eIF5A, such as N1-guanyl-1,7-diamine-heptane, ciclopirox, and deferiprone, are promising antivirals as well ( Fedorova et al, 2019 ; Mounce et al, 2016a ; Olsen and Connor, 2017 ; Olsen et al, 2018 ; Olsen et al, 2016 ). Here, we have shown DFMO or DENSpm administration caused polyamine depletion, and also exhibited antiviral activities against PRRSV, implying their potential as candidate polyamine-targeted agents for the future development of safe and efficient antivirals for PRRSV, and even SARS-CoV, MERS-CoV, SARS-CoV-2, individually, or in combination with other antiviral drugs.…”

Section: Discussionmentioning

confidence: 99%

Polyamine regulation of porcine reproductive and respiratory syndrome virus infection depends on spermidine-spermine acetyltransferase 1

Zhou

Hou

Fang

et al. 2020

Veterinary Microbiology

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Section: Discussionmentioning

confidence: 99%

Polyamine regulation of porcine reproductive and respiratory syndrome virus infection depends on spermidine-spermine acetyltransferase 1

Zhou

Hou

Fang

et al. 2020

Veterinary Microbiology

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“…Furthermore, high-throughput metabolic analysis of ∆Np73 −/− mice neurons showed slightly reduced glycolysis and reduced amounts of membrane phospholipids, long-chain fatty acids, sphingolipids [254], N-acetylaspartylglutamate, and neurotransmitter glycine, suggesting a delay in neuronal differentiation [251]. Interestingly, inhibition of polyamine catabolism decreases the ∆Np73/TAp73 ratio in favor of TAp73 and restores sensitivity of the monocytic leukemic cells THP-1 to doxorubicin [255].…”

Section: Biological Activity and Functions Of The P73 Isoformsmentioning

confidence: 97%

p53/p73 Protein Network in Colorectal Cancer and Other Human Malignancies

Horvat

Tadijan

Vlašić

et al. 2021

Cancers

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The p53 tumor suppressor protein is crucial for cell growth control and the maintenance of genomic stability. Later discovered, p63 and p73 share structural and functional similarity with p53. To understand the p53 pathways more profoundly, all family members should be considered. Each family member possesses two promoters and alternative translation initiation sites, and they undergo alternative splicing, generating multiple isoforms. The resulting isoforms have important roles in carcinogenesis, while their expression is dysregulated in several human tumors including colorectal carcinoma, which makes them potential targets in cancer treatment. Their activities arise, at least in part, from the ability to form tetramers that bind to specific DNA sequences and activate the transcription of target genes. In this review, we summarize the current understanding of the biological activities and regulation of the p53/p73 isoforms, highlighting their role in colorectal tumorigenesis. The analysis of the expression patterns of the p53/p73 isoforms in human cancers provides an important step in the improvement of cancer therapy. Furthermore, the interactions among the p53 family members which could modulate normal functions of the canonical p53 in tumor tissue are described. Lastly, we emphasize the importance of clinical studies to assess the significance of combining the deregulation of different members of the p53 family to define the outcome of the disease.

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“…It was found also that the DNp73 isoform occurs directly in sites of DNA damage, interacts with the 53BP1 sensory protein, and inhibits ATM activation and subsequent p53 phosphorylation, thus affecting p53-dependent apoptosis [ 110 ]. Thus, certain p73 isoforms possess tumor suppressor proteins, while other isoforms act as carcinogenic proteins, and the isoform balance determines the cell fate [ 111 – 113 ].…”

Section: Cytomegalovirus Can Decrease the Chemotherapy Sensitivity By...mentioning

confidence: 99%

“…In some cases, HCMV can change the balance between the tumor suppressor and carcinogenic p73 isoforms, and a predominance of the truncated isoforms facilitates the anticancer drug resistance [ 113 – 115 ]. HCMV infection was observed to activate the molecular pathways that induce expression of the E2F1 transcription factor [ 115 ], which is capable of both activating and inhibiting p73 [ 116 ].…”

Section: Cytomegalovirus Can Decrease the Chemotherapy Sensitivity By...mentioning

confidence: 99%

“…It is of interest that the observed shift in TA/DN isoforms is not associated with changes in isoform mRNA levels in HCMV-infected cancer cell cultures, possibly because transcription of both isoforms in cancer cells is substantially higher than in normal tissues [ 113 ]. Transcription of the DNp73 isoform is possibly maximal, which is consistent with hypomethylation of the internal promoter in lung cancer [ 124 ] and neuroblastoma [ 125 ] cells.…”

Section: Cytomegalovirus Can Decrease the Chemotherapy Sensitivity By...mentioning

confidence: 99%

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Mechanisms of Survival of Cytomegalovirus-Infected Tumor Cells

2022

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Human cytomegalovirus (HCMV) DNA and proteins are often detected in malignant tumors, warranting studies of the role that HCMV plays in carcinogenesis and tumor progression. HCMV proteins were shown to regulate the key processes involved in tumorigenesis. While HCMV as an oncogenic factor just came into focus, its ability to promote tumor progression is generally recognized. The review discusses the viral factors and cell molecular pathways that affect the resistance of cancer cells to therapy. CMV inhibits apoptosis of tumor cells, that not only promotes tumor progression, but also reduces the sensitivity of cells to antitumor therapy. Autophagy was found to facilitate either cell survival or cell death in different tumor cells. In leukemia cells, HCMV induces a “protective” autophagy that suppresses apoptosis. Viral factors that mediate drug resistance and their interactions with key cell death pathways are necessary to further investigate in order to develop agents that can restore the tumor sensitivity to anticancer drugs.

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Inhibitor of polyamine catabolism MDL72.527 restores the sensitivity to doxorubicin of monocytic leukemia Thp-1 cells infected with human cytomegalovirus

Cited by 7 publications

References 48 publications

Polyamine regulation of porcine reproductive and respiratory syndrome virus infection depends on spermidine-spermine acetyltransferase 1

Polyamine regulation of porcine reproductive and respiratory syndrome virus infection depends on spermidine-spermine acetyltransferase 1

p53/p73 Protein Network in Colorectal Cancer and Other Human Malignancies

Mechanisms of Survival of Cytomegalovirus-Infected Tumor Cells

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