A recombinant cell-permeable p53 fusion protein is selectively stabilized under hypoxia and inhibits tumor cell growth

Zhao, Yu; Wu, Jingyu; Wu, Shaoping; Jia, Peiyuan; Tong, Ying; Wu, Xumin; Wang, Yuxia

doi:10.1016/j.canlet.2009.01.030

Cited by 12 publications

(8 citation statements)

References 27 publications

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“…A similar system was also reported by Yu and co-workers, of which a recombinant cell-permeable p53 fusion protein containing ODD was shown to remain stable in hypoxia cells and inhibited tumor cell growth [99]. …”

Section: How To Curb the “Trojan Horse”mentioning

confidence: 64%

Curb challenges of the “Trojan Horse” approach: Smart strategies in achieving effective yet safe cell-penetrating peptide-based drug delivery

Huang

Jiang

Wang

et al. 2013

Advanced Drug Delivery Reviews

184

132

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Cell-penetrating peptide (CPP)-mediated intracellular drug delivery system, often specifically termed as “the Trojan horse approach”, has become the “holy grail” in achieving effective delivery of macromolecular compounds such as proteins, DNA, siRNAs, and drug carriers. It is characterized by the unique cell- (or receptor-), temperature-, and payload-independent mechanisms, therefore offering potent means to improve poor cellular uptake of a variety of macromolecular drugs. Nevertheless, this “Trojan horse” approach also acts like a double-edged sword, causing serious safety and toxicity concerns to normal tissues or organs for in vivo application, due to lack of target selectivity of the powerful cell penetrating activity. To overcome this problem of potent yet non-selective penetration vs. targeting delivery, a number of “smart” strategies have been developed in recent years, including controllable CPP-based drug delivery systems based on various stimuli-responsive mechanisms. This review article provides a fundamental understanding of these smart systems, as well as a discussion of their real-time in vivo applicability.

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Section: How To Curb the “Trojan Horse”mentioning

confidence: 64%

Curb challenges of the “Trojan Horse” approach: Smart strategies in achieving effective yet safe cell-penetrating peptide-based drug delivery

Huang

Jiang

Wang

et al. 2013

Advanced Drug Delivery Reviews

184

132

View full text Add to dashboard Cite

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“…BC003596) was fused and cloned into the pET28a vector. p53 cDNA was prepared from human embryonic total RNA by following the cDNA synthesis protocol (Promega, USA) and amplified by PCR [17]. GnRH and GnRH III fragments were introduced with primers GnRH P1, GnRH P2, GnRH III P1 and GnRH III P2 by PCR using pET28a-p53 as a template (Table 1).…”

Section: Methodsmentioning

confidence: 99%

The Novel Fusion Proteins, GnRH-p53 and GnRHIII-p53, Expression and Their Anti-Tumor Effect

Jia¹,

Zhao²,

et al. 2013

PLoS ONE

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p53, one of the most well studied tumor suppressor factor, is responsible to a variety of damage owing to the induction of apoptosis and cell cycle arrest in the tumor cells. More than 50% of human tumors contain mutation or deletion of p53. Gonadotrophin-releasing hormone (GnRH), as the ligand of Gonadotrophin-releasing hormone receptor (GnRH-R), was used to deliver p53 into tumor cells. The p53 fusion proteins GnRH-p53 and GnRH iii-p53 were expressed and their targeted anti-tumor effects were determined. GnRH mediates its fusion proteins transformation into cancer cells. The intracellular delivery of p53 fusion proteins exerted the inhibition of the growth of H1299 cells in vitro and the reduction of tumor volume in vivo. Their anti-tumor effect was functioned by the apoptosis and cell cycle arrest induced by p53. Hence, the fusion protein could be a novel protein drug for anti-tumor therapy.

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“…The mechanism of RDP-p53 induced cell death p53 gene is regarded as the ''guardian of the genome'', and encoding product p53 protein can inhibit or kill the tumor cells by various ways (Hansen et al, 2007;Yu et al, 2009;Yamada, 2013;Yan et al, 2012) including up-regulation of the expression of pro-apoptotic gene, down-regulation of the expression of anti-apoptotic gene for induction apoptosis, and prevention of cell cycle entry into M phase from G2 phase (Choi & Kim, 2009). In this study, to determine the anticancer mechanism of RDP-p53, the proteins were added into the media of SH-SY5Y cells for a certain time.…”

Section: Rdp-p53 Obviously Inhibited Sh-sy5y Cell Proliferationmentioning

confidence: 99%

A novel cell-permeable RDP-p53 fusion protein for specific inhibition on the growth of cancerous neural cells

Zhang

2015

Drug Delivery

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Objective: There is 25-35% mutation rate of p53 in cancerous neural cells and this rate reaches 70-76% in glioma cell line. Complement of wild-type p53 has become a potential strategy for protein therapy of cancerous neural cells. Here we investigated the feasibility of a novel RDP-p53 fusion protein for anti-proliferation of cancerous neural cell and the possible mechanism, which would provide an effective approach for targeted delivery of p53 protein to treat cancerous neural cells. Methods: The RDP-p53 fusion proteins are expressed in Escherichia coli, and they are labeled with FITC and rhodamine B by chemical modification. The fluorescence-labeled proteins are added to human hepatocellular carcinoma cells (HepG-2) and human neuroblastoma cells (SH-SY5Y) in order to investigate the possibility of RDP enhancing the cell uptake efficiency into neural cells as a cell-permeable carrier. The inhibitory effect of RDP-p53 on SH-SY5Y and human glioma cells (U251) was evaluated by MTT assay. Moreover, the anti-proliferation mechanism of RDP-p53 was determined by Apoptosis and Necrosis Assay Kit and flow cytometric analysis. Results:The results showed that RDP-p53 could enter SH-SY5Y cells with high efficiency and selectively inhibit the growth of cancerous neural cells, including SH-SY5Y and U251. Also, cell apoptosis pathway and cell-cycle arrest at the G2/M phase were associated with the inhibition mechanism of RDP-p53 according to the data of flow cytometric analysis. Conclusions: RDP-p53 could be a novel antitumor candidate for targeting treatment of cancerous neural cells.

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A recombinant cell-permeable p53 fusion protein is selectively stabilized under hypoxia and inhibits tumor cell growth

Cited by 12 publications

References 27 publications

Curb challenges of the “Trojan Horse” approach: Smart strategies in achieving effective yet safe cell-penetrating peptide-based drug delivery

Curb challenges of the “Trojan Horse” approach: Smart strategies in achieving effective yet safe cell-penetrating peptide-based drug delivery

The Novel Fusion Proteins, GnRH-p53 and GnRHIII-p53, Expression and Their Anti-Tumor Effect

A novel cell-permeable RDP-p53 fusion protein for specific inhibition on the growth of cancerous neural cells

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