Cytotoxicity, intracellular distribution and uptake of doxorubicin and doxorubicin coupled to cell-penetrating peptides in different cell lines: A comparative study

Aroui, Sonia; Brahim, Souhir; Waard, Michel De; Kénani, Abderraouf

doi:10.1016/j.bbrc.2009.11.073

Cited by 103 publications

(95 citation statements)

References 23 publications

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“…Novel CPP drug constructs, such as CPP Dox conjugates, showed an enormous potential to increase the properties of many chemotherapeutic drugs. Conjugates of Tat and penetratin with the chemotherapeutic drug doxorubicin demonstrated higher apoptotic efficiency compared with free Dox in different cell lines, which seems very promising for cancer treatment (Aroui et al, 2010). For example, the chitosan/doxorubicin/Tat hybrid displayed a more efficient cell internalization compared with free doxorubicin or chitosan/doxorubicin complex without Tat and yielded significantly higher antitumor effects (Shin et al, 2014).…”

Section: Application Of Cpps In Medicine and Biotechnologymentioning

confidence: 99%

Viral and Other Cell-Penetrating Peptides as Vectors of Therapeutic Agents in Medicine

Durzyńska

Przysiecka

Nawrot

et al. 2015

J Pharmacol Exp Ther

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Efficient delivery of heterologous molecules for treatment of cells is a great challenge in modern medicine and pharmacology. Cellpenetrating peptides (CPPs) may improve efficient delivery of a wide range of macromolecular cargos, including plasmid DNA, small interfering RNA, drugs, nanoparticulate pharmaceutical carriers, and anticancer drugs. In this paper, we present the history of CPPs' discovery with special attention drawn to sequences of viral origin. We also describe different CPP families with regard to their physicochemical properties and numerous mechanisms of CPP cell uptake by direct penetration and endocytotic pathways. A detailed description is focused on formation of carrier-cargo complexes, which are needed for practical use of CPPs in medicine and biotechnology. Examples of successful application of CPPs in treatment of human diseases are also presented, including decreased tumor growth and induction of cancer cell death. Finally, we review modern design approaches to novel CPPs and prediction of their activity. To sum up, the current review presents a thorough and up-to-date knowledge of CPPs and may be a valuable source of information for researchers in pharmacology designing new therapeutic agents.

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Section: Application Of Cpps In Medicine and Biotechnologymentioning

confidence: 99%

Viral and Other Cell-Penetrating Peptides as Vectors of Therapeutic Agents in Medicine

Durzyńska

Przysiecka

Nawrot

et al. 2015

J Pharmacol Exp Ther

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“…Studies that were undertaken to demonstrate the ability of MCa to reach its target showed that (i) MCa triggers Ca 2ϩ release from the SR a few seconds after its application in the extracellular medium (5) and (ii) intracellular accumulation of fluorescent-streptavidin occurs if it incubated first with biotinylated MCa (10). Since these pioneering studies, MCa or analogues thereof proved powerful vectors for the cell entry of proteins, peptides (11), nanoparticles, or drugs such as doxorubicin (12)(13)(14)(15). Although the mode of cell penetration of MCa may vary according to cargo nature, cell type, or chemical linkage employed, the data gathered so far suggest that the peptide may enter cells according to two priming steps onto the plasma membrane: first an interaction with proteoglycans with an affinity in the micromolar range, followed by a second interaction with negatively charged lipids which occurs with greater affinity (16,17).…”

Section: Maurocalcine (Mca)mentioning

confidence: 99%

Small Efficient Cell-penetrating Peptides Derived from Scorpion Toxin Maurocalcine

Poillot

Bichraoui

Tisseyre

et al. 2012

Journal of Biological Chemistry

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Background: This study aimed at developing a new set of maurocalcine-derived cell-penetrating peptides from truncation. Results: Several truncated peptides were designed and evaluated for Cy5 dye cell penetration. Conclusion: All truncated peptides are competitive cell-penetrating peptides, many of them comparing favorably well with TAT. Significance: Maurocalcine-derived truncated cell-penetrating peptides differ in their properties, enlarging the potential fields of applications.

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“…Intracellular doxorubicin was detected by confocal fluorescence microscopy on a Leica SP5 confocal microscope, using excitation and emission wavelengths of 470 and 590 nm (29). Doxorubicin fluorescence was quantitated by flow cytometry on an EPICS Coulter analyzer, using the above excitation and emission settings.…”

Section: Doxorubicin Detectionmentioning

confidence: 99%

Identification of Aldo-Keto Reductase AKR1B10 as a Selective Target for Modification and Inhibition by Prostaglandin A1: Implications for Antitumoral Activity

et al. 2011

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Cyclopentenone prostaglandins (cyPG) are reactive eicosanoids that may display anti-inflammatory and antiproliferative actions, possibly offering therapeutic potential. Here we report the identification of members of the aldo-keto reductase (AKR) family as selective targets of the cyPG prostaglandin A 1 (PGA 1 ). AKR enzymes metabolize aldehydes and drugs containing carbonyl groups and are involved in inflammation and tumorigenesis. Thus, these enzymes represent a class of targets to develop small molecule inhibitors with therapeutic activity. Molecular modeling studies pointed to the covalent binding of PGA 1 to Cys299, close to the active site of AKR, with His111 and Tyr49, which are highly conserved in the AKR family, playing a role in PGA 1 orientation. Among AKR enzymes, AKR1B10 is considered as a tumor marker and contributes to tumor development and chemoresistance. We validated the direct modification of AKR1B10 by biotinylated PGA 1 (PGA 1 -B) in cells, and confirmed that mutation of Cys299 abolishes PGA 1 -B incorporation, whereas substitution of His111 or Tyr49 reduced the interaction. Modification of AKR1B10 by PGA 1 correlated with loss of enzymatic activity and both effects were increased by depletion of cellular glutathione. Moreover, in lung cancer cells PGA 1 reduced tumorigenic potential and increased accumulation of the AKR substrate doxorubicin, potentiating cell-cycle arrest induced by this chemotherapeutic agent. Our findings define PGA 1 as a new AKR inhibitor and they offer a framework to develop compounds that could counteract cancer chemoresistance. Cancer Res; 71(12); 4161-71. Ó2011 AACR.

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Cytotoxicity, intracellular distribution and uptake of doxorubicin and doxorubicin coupled to cell-penetrating peptides in different cell lines: A comparative study

Cited by 103 publications

References 23 publications

Viral and Other Cell-Penetrating Peptides as Vectors of Therapeutic Agents in Medicine

Viral and Other Cell-Penetrating Peptides as Vectors of Therapeutic Agents in Medicine

Small Efficient Cell-penetrating Peptides Derived from Scorpion Toxin Maurocalcine

Identification of Aldo-Keto Reductase AKR1B10 as a Selective Target for Modification and Inhibition by Prostaglandin A1: Implications for Antitumoral Activity

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