The Membrane-Lytic Peptides K8L9 and Melittin Enter Cancer Cells via Receptor Endocytosis following Subcytotoxic Exposure

Kohno, Masayuki; Horibe, Tomohisa; Ohara, Koji; Ito, Shinji; Kawakami, Koji

doi:10.1016/j.chembiol.2014.09.008

Cited by 32 publications

(38 citation statements)

References 60 publications

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“…Interestingly, SV13-PV was also shown to form spherical nanoparticle-like structures prior cell entry [122]. Another example is the K8L9, which is an AMP at high concentrations, however, penetrates the cells at subcytotoxic doses via neuropilin-1 and LRP-1 receptors [116].…”

Section: Uptake Pathways Of Cpp and Nucleic Acid Conjugates And Nanopmentioning

confidence: 98%

“…Interestingly, an antimicrobial peptide (K8L9) was also shown to taken up into the cells via neuropilin-1 and low-density lipoprotein-related protein receptor 1 (LRP1) at subcytotoxic concentrations [116], demonstrating even further overlap between the two classes of molecules (CPPs and AMPs).…”

Section: Uptake Pathways Of Cpp and Nucleic Acid Conjugates And Nanopmentioning

confidence: 98%

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Peptides for nucleic acid delivery

Lehto

Ezzat

Wood

et al. 2016

Advanced Drug Delivery Reviews

184

132

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Nucleic acids and their synthetic oligonucleotide (ON) analogs are a group of gene therapeutic compounds which hold enormous clinical potential. Despite their undoubted potential, clinical translation of these molecules, however, has been largely held back by their limited bioavailability in the target tissues/cells. To overcome this, many different drug delivery systems have been devised. Among others, short delivery peptides, called cell-penetrating peptides (CPPs), have been demonstrated to allow for efficient delivery of nucleic acids and their ON analogs, in both cell culture and animal models. In this review, we provide brief overview of the latest advances in nucleic acid delivery with CPPs, covering the two main vectorization strategies, covalent conjugation and nanoparticle formation-based approach. In conclusion, CPP-based drug delivery systems have the capacity to overcome the hurdle of delivery and thus have the potential to facilitate the clinical translation of nucleic acid-based therapeutics.

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Section: Uptake Pathways Of Cpp and Nucleic Acid Conjugates And Nanopmentioning

confidence: 98%

Section: Uptake Pathways Of Cpp and Nucleic Acid Conjugates And Nanopmentioning

confidence: 98%

Peptides for nucleic acid delivery

Lehto

Ezzat

Wood

et al. 2016

Advanced Drug Delivery Reviews

184

132

View full text Add to dashboard Cite

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“…Melittin, is the main component of honey bee venom and has demonstrated a variety of biological and pharmacological applications [12,13]. It has natural anti-bacterial, anti-viral, and anti-inflammatory properties [12,13].…”

Section: Introductionmentioning

confidence: 99%

Metabolomic Profiling of the Effects of Melittin on Cisplatin Resistant and Cisplatin Sensitive Ovarian Cancer Cells Using Mass Spectrometry and Biolog Microarray Technology

et al. 2016

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In the present study, liquid chromatography-mass spectrometry (LC-MS) was employed to characterise the metabolic profiles of two human ovarian cancer cell lines A2780 (cisplatin-sensitive) and A2780CR (cisplatin-resistant) in response to their exposure to melittin, a cytotoxic peptide from bee venom. In addition, the metabolomics data were supported by application of Biolog microarray technology to examine the utilisation of carbon sources by the two cell lines. Data extraction with MZmine 2.14 and database searching were applied to provide metabolite lists. Principal component analysis (PCA) gave clear separation between the cisplatin-sensitive and resistant strains and their respective controls. The cisplatin-resistant cells were slightly more sensitive to melittin than the sensitive cells with IC50 values of 4.5 and 6.8 μg/mL respectively, although the latter cell line exhibited the greatest metabolic perturbation upon treatment. The changes induced by melittin in the cisplatin-sensitive cells led mostly to reduced levels of amino acids in the proline/glutamine/arginine pathway, as well as to decreased levels of carnitines, polyamines, adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD+). The effects on energy metabolism were supported by the data from the Biolog assays. The lipid compositions of the two cell lines were quite different with the A2780 cells having higher levels of several ether lipids than the A2780CR cells. Melittin also had some effect on the lipid composition of the cells. Overall, this study suggests that melittin might have some potential as an adjuvant therapy in cancer treatment.

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“…The eHSPs, particularly eHSP70, have been exploited for entry by rotavirus, reovirus and hepatitis B virus into host cells [41,42,43,44]. In an analogous manner, eHSPs are the membrane receptor for a number of CPPs [45,46]. The eHSP-CPP complex may also be taken up by antigen-presenting cells (APCs), such as dendritic cells.…”

Section: Potential Of Gv1001 As a Heat Shock Protein (Hsp)-mediatementioning

confidence: 99%

The Telomerase-Derived Anticancer Peptide Vaccine GV1001 as an Extracellular Heat Shock Protein-Mediated Cell-Penetrating Peptide

Kim

Seo

Lee

et al. 2016

IJMS

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Cell-penetrating peptides (CPPs), which can facilitate the transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular delivery of macromolecules. GV1001, a peptide derived from a reverse-transcriptase subunit of telomerase (hTERT) and developed as a vaccine against various cancers, reportedly has unexpected CPP properties. Unlike typical CPPs, such as the HIV-1 TAT peptide, GV1001 enabled the cytosolic delivery of macromolecules such as proteins, DNA and siRNA via extracellular heat shock protein 90 (eHSP90) and 70 (eHSP70) complexes. The eHSP-GV1001 interaction may have biological effects in addition to its cytosolic delivery function. GV1001 was originally designed as a major histocompatibility complex (MHC) class II-binding cancer epitope, but its CPP properties may contribute to its strong anti-cancer immune response relative to other telomerase peptide-based vaccines. Cell signaling via eHSP-GV1001 binding may lead to unexpected biological effects, such as direct anticancer or antiviral effects. In this review, we focus on the CPP effects of GV1001 bound to eHSP90 and eHSP70.

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The Membrane-Lytic Peptides K8L9 and Melittin Enter Cancer Cells via Receptor Endocytosis following Subcytotoxic Exposure

Cited by 32 publications

References 60 publications

Peptides for nucleic acid delivery

Peptides for nucleic acid delivery

Metabolomic Profiling of the Effects of Melittin on Cisplatin Resistant and Cisplatin Sensitive Ovarian Cancer Cells Using Mass Spectrometry and Biolog Microarray Technology

The Telomerase-Derived Anticancer Peptide Vaccine GV1001 as an Extracellular Heat Shock Protein-Mediated Cell-Penetrating Peptide

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