Apoptin as a Potential Viral Gene Oncotherapeutic Agent

Singh, Prafull; Tiwari, Ashok Kumar; Rajmani, R. S.; Kumar, Girish; Chaturvedi, Uttara; Saxena, Lovleen; Saxena, Shikha; Doley, Juwar; Sahoo, Aditya Prasad; Santra, Lakshman; Saxena, M.; Kumar, Satish; Sharma, Bhaskar

doi:10.1007/s12010-015-1567-5

Cited by 12 publications

(10 citation statements)

References 34 publications

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“…In all the experiments carried out, the cell nuclei were stained in red using the Hoechst method [62]. Hoechst dye, which binds to the minor goove of DNA, has been extensively used by many laboratories for studying nuclear changes occurring during apoptosis [85]. As depicted in Fig.…”

Section: Expression Of At-iii In Differentiating Primary Culture Of Bmentioning

confidence: 99%

Caspases and Thrombin Activity Regulation by Specific Serpin Inhibitors in Bovine Skeletal Muscle

Gagaoua

Hafid

Boudida

et al. 2015

Appl Biochem Biotechnol

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In living cells, after activation, protein inhibitors constitute the last step of proteases activity regulation. This review intends to provide original information about a group of bovine muscle serine proteases inhibitors belonging to the Serpin superfamily and characterized at the gene and protein level. This report is the only one and the first to provide much information on this group of proteases inhibitors of the serpin type and their potential biological functions. Amongst the eight genes identified in bovine, three serpins were purified from the muscle tissue and characterized. These are two members of the bovSERPINA3 family, i.e., bovSERPINA3-1 and A3-3, and the last one is antithrombin III (AT-III or BovSERPINC1). BovSERPINA3 family comprises at least eight protein members encoded by different genes mapped on chromosome 7q23-q26 cluster. BovSERPINA3-1 and A3-3 were shown to locate within muscle cells and are cross-class inhibitors strongly active against trypsin as well as against human initiator and effector caspases 8 and 3. They constitute a key apoptosis control in mammals. They were thus expressed in proliferating and confluent myoblasts phases where cells must be alive but not in myotubes. Antithrombin III inhibits trypsin and, in a heparin dependent manner, thrombin. AT-III and its mRNA were expressed in muscle cells and in differentiating primary myoblasts in culture.

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Section: Expression Of At-iii In Differentiating Primary Culture Of Bmentioning

confidence: 99%

Caspases and Thrombin Activity Regulation by Specific Serpin Inhibitors in Bovine Skeletal Muscle

Gagaoua

Hafid

Boudida

et al. 2015

Appl Biochem Biotechnol

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“…For example, the pro-apoptosis activity of apoptin involves the nuclear sequence (NLS), the NES, and the phosphorylation of amino acid 108. The level of specifically targeted tumor apoptosis was decreased slightly by the ADP structure without nuclear sequences and no phosphorylation of amino acid 108 [ 9 , 16 , 17 ]. We hypothesized that ADP would not exhibit the ability to target tumor cells.…”

Section: Discussionmentioning

confidence: 99%

A peptide derived from apoptin inhibits glioma growth

et al. 2017

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Glioblastoma (GBM) is associated with poor prognosis due to its resistance to surgery, irradiation, and conventional chemotherapy. Thus, efficient therapeutic approaches for the treatment of GBM are urgently needed. HSP70 is an antiapoptotic protein that participates in the inhibition of both mitochondrial and membrane receptor apoptosis pathways and is highly expressed in glioma tissues. Here, we investigated a derivative of apoptin; specifically, a chicken anemia viral protein with selective toxicity toward cancer cells that can inhibit hyperactive molecules, including HSP70. Our earlier studies demonstrated that apoptin directly binds to the promoter of HSP70 and inhibits HSP70 transcription, which contributes to HSP70 downregulation. This study provides the first demonstration of the therapeutic potential of an apoptin-derived peptide for the treatment of GBM by identifying the minimal region of the apoptin domain required for interaction with the heat-shock element (HSE). This apoptin-derived peptide (ADP) inhibits glioma cell proliferation and tumor growth as well as exhibits an increased ability to promote apoptosis in GBM cells compared with rapamycin and temozolomide. ADP treatment inhibited xenograft tumor growth and increased the overall health and survival of nude mice implanted with GBM cells. These effects were measured in tumors obtained from cell lines and were observed in both intracranial and subcutaneous xenografts. In conclusion, we provide the first demonstration that ADP has therapeutic potential for the treatment of human GBM. Specifically, this study suggests that ADP is a potent candidate for drug development based on its favorable toxicity and pharmacokinetic profiles as well as its time- and cost-saving benefits.

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“…It also transformed cells without affecting normal cells. In a recent study, apoptin induced apoptosis in HeLa cells through a caspase-dependent intrinsic pathway, independent of p53 activation [89]. Apoptin is found in the nucleus of tumor cells, whereas it is found in the cytoplasm in normal cells.…”

Section: Suicide Gene Therapymentioning

confidence: 94%

Targeted Gene Delivery Therapies for Cervical Cancer

Ayén

Martínez

Boulaiz

2020

Cancers

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Despite being largely preventable through early vaccination and screening strategies, cervical cancer is the most common type of gynecological malignancy worldwide and constitutes one of the leading causes of cancer deaths in women. Patients with advanced or recurrent disease have a very poor prognosis; hence, novel therapeutic modalities to improve clinical outcomes in cervical malignancy are needed. In this regard, targeted gene delivery therapy is presented as a promising approach, which leads to the development of multiple strategies focused on different aspects. These range from altered gene restoration, immune system potentiation, and oncolytic virotherapy to the use of nanotechnology and the design of improved and enhanced gene delivery systems, among others. In the present manuscript, we review the current progress made in targeted gene delivery therapy for cervical cancer, the advantages and drawbacks and their clinical application. At present, multiple targeted gene delivery systems have been reported with encouraging preclinical results. However, the translation to humans has not yet shown a significant clinical benefit due principally to the lack of efficient vectors. Real efforts are being made to develop new gene delivery systems, to improve tumor targeting and to minimize toxicity in normal tissues.

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Apoptin as a Potential Viral Gene Oncotherapeutic Agent

Cited by 12 publications

References 34 publications

Caspases and Thrombin Activity Regulation by Specific Serpin Inhibitors in Bovine Skeletal Muscle

Caspases and Thrombin Activity Regulation by Specific Serpin Inhibitors in Bovine Skeletal Muscle

A peptide derived from apoptin inhibits glioma growth

Targeted Gene Delivery Therapies for Cervical Cancer

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