Cell-penetrating peptides modulate the vascular action of phenylephrine

Kocić, Ivan; Ruczyński, Jarosław; Szczepańska, Renata; Olkowicz, Mariola; Parfianowicz, Brygida; Rusiecka, Izabela; Rekowski, Piotr

doi:10.1016/s1734-1140(11)70416-9

Cited by 5 publications

(3 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The potential role of CPPs, as carriers for different molecules, including drugs is still a matter of considerable interest (Kocić et al 2011 ), particularly in cancer therapy. Their use may improve chemotherapeutic strategies for example such as prevention of the drug resistance evolution, increase in the ability of recognition of cancer cells (targeted therapy), and enhancement of the therapeutic response to the cargo.…”

Section: Introductionmentioning

confidence: 99%

Transportan 10 improves the anticancer activity of cisplatin

Rusiecka

Ruczyński

Alenowicz

et al. 2016

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

The aim of this paper was to examine whether cell-penetrating peptides (CPPs) such as transportan 10 (TP10) or protein transduction domain (PTD4) may improve the anticancer activity of cisplatin (cPt). The complexes of TP10 or PTD4 with cPt were used in the experiments. They were carried out on two non-cancer (HEK293 (human embryonic kidney) and HEL299 (human embryo lung)) and two cancer (HeLa (human cervical cancer) and OS143B (human osteosarcoma 143B)) cell lines. Both complexes were tested (MTT assay) with respect to their anticancer or cytotoxic actions. TAMRA (fluorescent dye)-stained preparations were visualized in a fluorescence microscope. The long-term effect of TP10 + cPt and its components on non-cancer and cancer cell lines was observed in inverted phase contrast microscopy. In the MTT test (cell viability assay), the complex of TP10 + cPt produced a more potent effect on the cancer cell lines (HeLa, OS143B) in comparison to that observed after separate treatment with TP10 or cPt. At the same time, the action of the complex and its components was rather small on non-cancer cell lines. On the other hand, a complex of another CPP with cPt, i.e., PTD4 + cPt, was without a significant effect on the cancer cell line (OS143B). The images of the fluorescent microscopy showed TAMRA-TP10 or TAMRA-TP10 + cPt in the interior of the HeLa cells. In the case of TAMRA-PTD4 or TAMRA-PTD4 + cPt, only the first compound was found inside the cancer cell line. In contrast, none of the tested compounds gained access to the interior of the non-cancer cells (HEK293, HEL299). Long-term incubation with the TP10 + cPt (estimated by inverted phase contrast microscopy) lead to an enhanced action of the complex on cell viability (decrease in the number of cells and change in their morphology) as compared with that produced by each single agent. With regard to the tested CPPs, only TP10 improved the anticancer activity of cisplatin if both compounds were used in the form of a complex. Additionally, the complex was relatively safe for non-cancer cells. What is more, TP10 also produced an anticancer effect on HeLa and OS143B cell lines.

show abstract

Section: Introductionmentioning

confidence: 99%

Transportan 10 improves the anticancer activity of cisplatin

Rusiecka

Ruczyński

Alenowicz

et al. 2016

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

show abstract

“…All peptides used in this study (Table 1) were synthesized in the Department of Chemistry of Biological Active Molecules, University of Gdansk, Poland, using the Fmoc strategy of solid-phase peptide synthesis as described previously [26]. Purification and analysis of the peptides were performed with the use of MALDI-TOF mass spectrometer.…”

Section: Cell Linesmentioning

confidence: 99%

Protein and siRNA delivery by transportan and transportan 10 into colorectal cancer cell lines

Wierzbicki

Kogut-Wierzbicka

Ruczyński

et al. 2015

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

Introduction. Cell penetrating peptides (CPPs) have the ability to translocate through cell membranes with high efficiency and therefore can introduce biological agents with pharmaceutical properties into the cell. Transportan (TP) and its shorter analog transportan 10 (TP10) are among the best studied CPPs, however, their effects on viability of and cargo introduction into colorectal cancer (CRC) cells have yet not been investigated. The aim of our study was to evaluate the cytotoxic effects of TP and TP10 on representative CRC lines and the efficiency of protein (streptavidin) and siRNA cargo delivery by TP-biotinylated derivatives (TP-biot). Material and methods. HT29 (early stage CRC model) and HCT116 (metastatic CRC model) cell lines were incubated with TP, TP10, TP-biot1, TP-biot13 and TP10-biot1. The effects of studied CPPs on cell viability and cell cycle were assessed by MTT and annexin V assays. The uptake of streptavidin-FITC complex into cells was determined by flow cytometry and fluorescence microscopy, with the inhibition of cellular vesicle trafficking by brefeldin A. The efficiency of siRNA for SASH1 gene delivery was measured by quantitative PCR (qPCR). Results. Since up to 10 µM concentrations of each CPP showed no significant cytotoxic effect, the concentrations of 0.5-5 µM were used for further analyses. Within this concentration range none of the studied CPPs affected cell viability and cell cycle. The efficient and endocytosis-independent introduction of streptavidin-FITC complex into cells was observed for TP10-biot1 and TP-biot1 with the cytoplasmic location of the fluorescent cargo; decreased SASH1 mRNA level was noticed with the use of siRNA and analyzed CPPs. Conclusions. We conclude that TP, TP10 and their biotinylated derivatives can be used as efficient delivery vehicles of small and large cargoes into CRC cells.

show abstract

“…TP10 and its alkyne functionalized TP10 analogue (Prp-TP10) were synthesized by the solid-phase peptide synthesis with the use of automatic peptide synthesizer (Quartet, Protein Technologies Inc.) and Fmoc strategy. ,,,,− TentaGel S RAM resin (loading 0.25 mM/g) was used as the starting material. Fmoc protected amino acids were assembled as active derivatives with the use of a 3-fold molar excess of O -(benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) with the addition of N -hydroxybenzotriazole (HOBt) and N -methylmorpholine (molar ratio 1:1:2) in N,N -dimethylformamide (DMF) solution for 2 × 0.5 h.…”

Section: Materials and Methodsmentioning

confidence: 99%

TP10-Dopamine Conjugate as a Potential Therapeutic Agent in the Treatment of Parkinson’s Disease

et al. 2019

Self Cite

View full text Add to dashboard Cite

Parkinson's disease (PD) is a common progressive neurodegenerative disorder for which the current treatment is not fully satisfactory. One of the major drawbacks of current PD therapy is poor penetration of drugs across the blood-brain barrier (BBB). In recent years, cell-penetrating peptides (CPPs) such as Tat, SynB, or TP10 have gained great interest due to their ability to penetrate cell membranes and to deliver different cargos to their targets including the central nervous system (CNS). However, there is no data with respect to the use of CPPs as drug carriers to the brain for the treatment of PD. In the presented research, the covalent TP10-dopamine conjugate was synthesized and its pharmacological properties were characterized in terms of its ability to penetrate the BBB and anti-parkinsonian activity. The results showed that dopamine (DA) in the form of a conjugate with TP10 evidently gained access to the brain tissue, exhibited low susceptibility to O-methylation reaction by catechol-O-methyltransferase (lower than that of DA), possessed a relatively high affinity to both dopamine D 1 and D 2 receptors (in the case of D 1 , a much higher than that of DA), and showed antiparkinsonian activity (higher than that of L-DOPA) in the MPTP-induced preclinical animal model of PD. The presented results prove that the conjugation of TP10 with DA may be a good starting point for the development of a new strategy for the treatment of PD.

show abstract

Cell-penetrating peptides modulate the vascular action of phenylephrine

Cited by 5 publications

References 11 publications

Transportan 10 improves the anticancer activity of cisplatin

Transportan 10 improves the anticancer activity of cisplatin

Protein and siRNA delivery by transportan and transportan 10 into colorectal cancer cell lines

TP10-Dopamine Conjugate as a Potential Therapeutic Agent in the Treatment of Parkinson’s Disease

Contact Info

Product

Resources

About