Apoptin: Therapeutic Potential of an Early Sensor of Carcinogenic Transformation

Backendorf, Claude; Visser, Astrid E.; Boer, Albertus G. de; Zimmerman, R. M. E.; Visser, Mijke; Voskamp, Patrick; Zhang, Yinghui; Noteborn, Mathieu H. M.

doi:10.1146/annurev.pharmtox.48.121806.154910

Cited by 76 publications

(80 citation statements)

References 98 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Apoptin is a viral protein from the chicken anemia virus (CAV) which is able to induce apoptosis in tumor cells. This protein, with a molecular weight of 13,600 Da, is composed of 121 amino acids and contains 2 functional regions (13). In previous studies, the following merits of Apoptin in antitumor therapy were revealed: Apoptin is able to induce apoptosis in numerous types of malignant tumor cells (13); Apoptin is capable of killing tumor cells but not normal cells (4); Apoptin is able to induce high levels of apoptosis in tumor cells (14); the antitumor effect of Apoptin does not depend on the expression of p53 (15); Apoptin is able to induce high levels of apoptosis in tumor cells expressing the anti-apoptosis proteins Bcl-2 and Bcl-xL (16).…”

Section: Discussionmentioning

confidence: 99%

TAT-Apoptin induces apoptosis in the human bladder cancer EJ cell line and regulates Bax, Bcl-2, caspase-3 and survivin expression

Wang

Fan

et al. 2012

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. In order to identify the antitumor effect of TAT-Apoptin on the human bladder cancer EJ cell line and study its impact on the expression of the apoptosis-related genes bax, bcl-2, caspase-3 and survivin, the MTT assay, real-time quantitative PCR and western blot analysis were used in this study. The results of the MTT assay indicated that TAT-Apoptin was able to inhibit the proliferation of EJ cells in a dose-dependent manner. The expression of Bax, Bcl-2, Caspase-3 and Survivin mRNA and protein following the treatment of the EJ cells with TAT-Apoptin (0.1, 0.5, 1, 10, 50 and 100 µg/ml) for 24, 48 and 72 h was analyzed. Cell proliferation was significantly different after treatment with the various concentrations of TAT-Apoptin and the durations of treatment. The level of expression of Bcl-2 and Survivin in EJ cells decreased significantly, while that of Bax and Caspase-3 increased significantly at the mRNA and protein levels.

show abstract

Section: Discussionmentioning

confidence: 99%

TAT-Apoptin induces apoptosis in the human bladder cancer EJ cell line and regulates Bax, Bcl-2, caspase-3 and survivin expression

Wang

Fan

et al. 2012

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…Apoptin has been reported to induce the selective death of tumor cells derived from diverse tumors, whereas it does not induce apoptosis in nontransformed cells (3,48,59). The manner by which apoptin distinguishes between tumor and normal cells remains largely unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Apoptin is a small viral protein that was originally identified in chicken anemia virus and shows remarkable anticancer toxicity and selectivity (3,48,59). The tumor-selective cell death induced by apoptin has been demonstrated in a great number of tumor cells of different origins by the use of several techniques, including overexpression or introduction of cell-permeative apoptin constructs (8,13,24,51).…”

mentioning

confidence: 99%

Unscheduled Akt-Triggered Activation of Cyclin-Dependent Kinase 2 as a Key Effector Mechanism of Apoptin's Anticancer Toxicity

Maddika

Panigrahi

Wiecheć

et al. 2009

Molecular and Cellular Biology

View full text Add to dashboard Cite

Apoptin, a protein from the chicken anemia virus, has attracted attention because it specifically kills tumor cells while leaving normal cells unharmed. The reason for this tumor selectivity is unclear and depends on subcellular localization, as apoptin resides in the cytoplasm of normal cells but in the nuclei of transformed cells. It was shown that nuclear localization and tumor-specific killing crucially require apoptin's phosphorylation by an as yet unknown kinase. Here we elucidate the pathway of apoptin-induced apoptosis and show that it essentially depends on abnormal phosphatidylinositol 3-kinase (PI3-kinase)/Akt activation, resulting in the activation of the cyclin-dependent kinase CDK2. Inhibitors as well as dominant-negative mutants of PI3-kinase and Akt not only inhibited CDK2 activation but also protected cells from apoptin-induced cell death. Akt activated CDK2 by direct phosphorylation as well as by the phosphorylation-induced degradation of the inhibitor p27 Kip1 . Importantly, we also identified CDK2 as the principal kinase that phosphorylates apoptin and is crucially required for apoptin-induced cell death. Immortalized CDK2-deficient fibroblasts and CDK2 knockdown cells were markedly protected against apoptin. Thus, our results not only decipher the pathway of apoptin-induced cell death but also provide mechanistic insights for the selective killing of tumor cells.

show abstract

“…as protein or gene therapy. In any case, efficient systems are required to facilitate the delivery of apoptin to cancer cells or expression of apoptin within these cells [26][27][28][29][30] . The HIV TAT transduction domain has been successfully used to deliver apoptin into cancer cells [14] , and no apoptosis of normal cells (HUVECs) was observed with this TATapoptin fusion protein.…”

Section: Discussionmentioning

confidence: 99%

Secretory Transactivating Transcription-apoptin fusion protein induces apoptosis in hepatocellular carcinoma HepG2 cells

Han¹,

Ma²,

Lee³

et al. 2008

WJG

View full text Add to dashboard Cite

AIM:To determine whether SP-TAT-apoptin induces apoptosis and also maintains its tumor cell specificity. METHODS: In this study, we designed a secretory protein by adding a secretory signal peptide (SP) to the N terminus of Transactivating Transcription (TAT)-apoptin (SP-TAT-apoptin), to test the hypothesis that it gains an additive bystander effect as an anti-cancer therapy. We used an artificial human secretory SP whose amino acid sequence and corresponding cDNA sequence were generated by the SP hidden Markov model. RESULTS: In human liver carcinoma HepG2 cells, SP-TAT-apoptin expression showed a diffuse pattern in the early phase after transfection. After 48 h, however, it translocated into the nuclear compartment and caused massive apoptotic cell death, as determined by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and annexin-V binding assay. SP-TAT-apoptin did not, however, cause any cell death in non-malignant human umbilical vein endothelial cells (HUVECs). Most importantly, the conditioned medium from Chinese hamster ovary (CHO) cells transfected with SP-TAT-apoptin also induced significant cell death in HepG2 cells, but not in HUVECs. CONCLUSION: The data demonstrated that SP-TATapoptin induces apoptosis only in malignant cells, and its secretory property might greatly increase its potency once it is delivered in vivo for cancer therapy.

show abstract

Apoptin: Therapeutic Potential of an Early Sensor of Carcinogenic Transformation

Cited by 76 publications

References 98 publications

TAT-Apoptin induces apoptosis in the human bladder cancer EJ cell line and regulates Bax, Bcl-2, caspase-3 and survivin expression

TAT-Apoptin induces apoptosis in the human bladder cancer EJ cell line and regulates Bax, Bcl-2, caspase-3 and survivin expression

Unscheduled Akt-Triggered Activation of Cyclin-Dependent Kinase 2 as a Key Effector Mechanism of Apoptin's Anticancer Toxicity

Secretory Transactivating Transcription-apoptin fusion protein induces apoptosis in hepatocellular carcinoma HepG2 cells

Contact Info

Product

Resources

About