Cell-penetrating peptide-conjugated XIAP-inhibitory cyclic hexapeptides enter into Jurkat cells and inhibit cell proliferation

Abstract Background: Periodontitis irreversibly invades and destroys periodontal supporting tissues, loses the ability of periodontal regeneration and restoration, and eventually leads to tooth loosening and loss. periodontal ligament stem cells (PDLSCs) hold great promises for periodontal tissue regeneration which was the potential target of periodontitis treatment, siRNARANKL and oestrogen can help PDLSCs maintain normal function, however, it was very difficult for siRNARANKL and oestrogen to get into PDLSCs. Here, Cell penetrating peptide CADY was modified on the surface of siRNARANKL and oestrogen loaded mesoporous silica nanoparticles (MSNs) to carry them into Porphyromonas gingivalis infected PDLSCs, Then further affect the proliferation of PDLSCs. Methods: 120-150 nm Mesoporous silica nanoparticles (MSNs) was prepared, and the biocompatibility, loading capacity and drug release properity were tested; MSNs was modified by penetrating peptide CADY and the prepared MSNs/CADY was loaded with siRNARANKL and oestrogen; In vitro drug release of siRNARANKL/MSNs-CADY and oestrogen/MSNs-CADY was tested by using semi-permeable dialysis bag diffusion; Cellular uptake and internalization of FITC-Labeled MSNs and FITC-Labeled MSNs-CADY was observed by use of Laser confocal microscopy; Finally, the effect of siRNARANKL and oestrogen loaded MSNs-CADY on cell proliferation of Porphyromonas gingivalis infected human periodontal ligament stem cells was tested by MTT assay. Results: according to the results, MSNs-CADY with a concentration of 6.25-200 ug/mL have no toxic to PDLSCs; 24.6 mg oestrogen and 0.5 mM siRNARANKL can be loaded into 1mg of MSNs-CADY; and drug loaded MSNs-CADY nanodrug carriers can release siRNARANKL and oestrogen stably for at least 48 h; After modification with cell penetrating peptide CADY, more MSNs-CADY can be taken by PDLSCs. siRNARANKL/oestrogen/MSNs-CADY can increase the proliferation of PDLSCs significantly. Conclusion: siRNARANKL/oestrogen/MSNs-CADY constructed can significantly improve the cell proliferation of P-gingivalis infected PDLSCs, this nano drug carrier has the potential to be used in PDLSCs -based periodontitis treatment, this work provided a useful theoretical basis and therapeutic ideas for the treatment of periodontitis.

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Synthesis and Antiproliferative Activities of Conjugates of Paclitaxel and Camptothecin with a Cyclic Cell-Penetrating Peptide

Molecules ◽

10.3390/molecules24071427 ◽

2019 ◽

Vol 24 (7) ◽

pp. 1427 ◽

Cited By ~ 7

Author(s):

Naglaa Salem El-Sayed ◽

Amir Nasrolahi Shirazi ◽

Muhammad Imran Sajid ◽

Shang Eun Park ◽

Keykavous Parang ◽

...

Keyword(s):

Cell Proliferation ◽

Water Solubility ◽

Cyclic Peptide ◽

Solid Phase ◽

Parent Drug ◽

Hydroxyl Group ◽

Esterification Reaction ◽

Cell Penetrating Peptide ◽

Cell Penetrating ◽

Mcf 7

Cell-penetrating peptide [WR]5 has been previously shown to be an efficient molecular transporter for various hydrophilic and hydrophobic molecules. The peptide was synthesized using Fmoc/tBu solid-phase chemistry, and one arginine was replaced with one lysine to enable the conjugation with the anticancer drugs. Paclitaxel (PTX) was functionalized with an esterification reaction at the C2′ hydroxyl group of PTX with glutaric anhydride and conjugated with the cyclic peptide [W(WR)4K(βAla)] in DMF to obtain the peptide-drug conjugate PTX1. Furthermore, camptothecin (CPT) was modified at the C(20)-hydroxyl group through the reaction with triphosgene. Then, it was conjugated with two functionalized cyclic peptides through a formyl linker affording two different conjugates, namely CPT1 and CPT2. All the conjugates showed better water solubility as compared to the parent drug. The cytotoxicity assay of the drugs and their conjugates with the peptides were evaluated in the human breast cancer MCF-7 cell line. PTX inhibited cell proliferation by 39% while the PTX-peptide conjugate inhibited the proliferation by ~18% after 72 h incubation. On the other hand, CPT, CPT1, and CPT2 reduced the cell proliferation by 68%, 39%, and 62%, respectively, in the MCF-7 cell lines at 5 µM concentration after 72 h incubation.

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Tea Catechins Inhibit Cell Proliferation Through Hydrogen Peroxide-Dependent and -Independent Pathways in Human T lymphocytic Leukemia Jurkat Cells

Food Science and Technology Research ◽

10.3136/fstr.20.1245 ◽

2014 ◽

Vol 20 (6) ◽

pp. 1245-1249 ◽

Cited By ~ 4

Author(s):

Yue Tang ◽

Naomi Abe ◽

Hang Qi ◽

Beiwei Zhu ◽

Yoshiyuki Murata ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Cell Proliferation ◽

Lymphocytic Leukemia ◽

Jurkat Cells ◽

Tea Catechins ◽

Inhibit Cell Proliferation

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Ginsenoside Rh2 and Rg3 inhibit cell proliferation and induce apoptosis by increasing mitochondrial reactive oxygen species in human leukemia Jurkat cells

Molecular Medicine Reports ◽

10.3892/mmr.2017.6459 ◽

2017 ◽

Vol 15 (6) ◽

pp. 3591-3598 ◽

Cited By ~ 20

Author(s):

Ting Xia ◽

Ying-Nan Wang ◽

Chuan-Xin Zhou ◽

Li-Mei Wu ◽

Yong Liu ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Cell Proliferation ◽

Reactive Oxygen ◽

Jurkat Cells ◽

Human Leukemia ◽

Oxygen Species ◽

Ginsenoside Rh2 ◽

Mitochondrial Reactive Oxygen Species ◽

Inhibit Cell Proliferation

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Co-delivery of drug nanoparticles and siRNA mediated by a modified cell penetrating peptide for inhibiting cancer cell proliferation

RSC Advances ◽

10.1039/c4ra14827d ◽

2015 ◽

Vol 5 (26) ◽

pp. 20554-20556 ◽

Cited By ~ 6

Author(s):

Dafeng Chu ◽

Wen Xu ◽

Ran Pan ◽

P. Chen

Keyword(s):

Cell Proliferation ◽

Cell Growth ◽

Cancer Cell ◽

Cell Penetrating Peptide ◽

Cancer Cell Proliferation ◽

Cancer Cell Growth ◽

Drug Nanoparticles ◽

Cell Penetrating

Modified cell penetrating peptide can stabilize drug nanoparticles with improved efficacy and co-deliver siRNA inducing synergy on the inhibition of cancer cell growth.

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