Experimental local therapy of human melanoma with lytic magainin peptides

Soballe, Peter W.; Maloy, W L; Myrga, M L; Jacob, Leonard S.; Herlyn, Meenhard

doi:10.1002/ijc.2910600225

Cited by 71 publications

(47 citation statements)

References 19 publications

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“…Because the antiplasmodium activity paralleled the lytic activity, albeit 30-fold-higher concentrations were needed to lyse uninfected cells, we have undertaken the development of additional derivatives with greater selectivity. We have been guided by the following rationale: selective antimicrobial activity of peptides demonstrably depends on the membrane lipid composition (19,23,31). The lipid compositions of the host and parasite membrane are different (37).…”

Section: Vol 46 2002 Antiplasmodium Effects Of Dermaseptin S4 Derivmentioning

confidence: 99%

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In Vitro Antiplasmodium Effects of Dermaseptin S4 Derivatives

Dagan

Efron

Gaidukov

et al. 2002

Antimicrob Agents Chemother

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The 13-residue dermaseptin S4 derivative K 4 S4(1-13)a (P) was previously shown to kill intraerythrocytic malaria parasites through the lysis of the host cells. In this study, we have sought peptides that will kill the parasite without lysing the erythrocyte. To produce such peptides, 26 compounds of variable structure and size were attached to the N terminus of P and screened for antiplasmodium and hemolytic activities in cultures of Plasmodium falciparum. Results from this screen indicated that increased hydrophobicity results in amplified antiplasmodium effect, irrespective of the linearity or bulkiness of the additive. However, increased hydrophobicity also was generally associated with increased hemolysis, with the exception of two derivatives: propionyl-P (C3-P) and isobutyryl-P (iC4-P). Both acyl-peptides were more effective than P, with 50% growth inhibition at 3.8, 4.3, and 7.7 M, respectively. The antiparasitic effect was time dependent and totally irreversible, implying a cytotoxic effect. The peptides were also investigated in parallel for their ability to inhibit parasite growth and to induce hemolysis in infected and uninfected erythrocytes. Whereas the dose dependence of growth inhibition and hemolysis of infected cells overlapped when cells were treated with P, the acyl-peptides exerted 50% growth inhibition at concentrations that did not cause hemolysis. Noticeably, the acyl derivatives, but not P, were able to dissipate the parasite plasma membrane potential and cause depletion of intraparasite potassium under nonhemolytic conditions. These results clearly demonstrate that the acyl-peptides can affect parasite viability in a manner that is dissociated from lysis of the host cell. Overall, the data indicate the potential usefulness of this strategy for development of selective peptides as investigative tools and eventually as antimalarial agents.

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Section: Vol 46 2002 Antiplasmodium Effects Of Dermaseptin S4 Derivmentioning

confidence: 99%

“…Many antimicrobial peptides display a broad spectrum of activity that can kill or neutralize gram-negative and -positive bacteria, yeast and filamentous fungi, and some enveloped viruses, as well as many types of cancer cells (19,23,31). Yet, many of these peptides are quite inactive on normal eukaryotic cells.…”

mentioning

confidence: 99%

In Vitro Antiplasmodium Effects of Dermaseptin S4 Derivatives

Dagan

Efron

Gaidukov

et al. 2002

Antimicrob Agents Chemother

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“…Interestingly, several insect AMPs show cytotoxic effects against a broad range of cancer cell lines such as mouse myeloma, melanoma, lymphomas, leukemia, breast cancer and lung cancer (8)(9)(10)(11)(12). Coprisin belongs to the defensin family of insect AMPs, and has been identified from dung beetle, Copris tripartitus (13) and its analogue CopA3 showing cytotoxicity against cancer cell lines as well as strong antibacterial activity against microbes (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Anticancer activity of a synthetic peptide derived from harmoniasin, an antibacterial peptide from the ladybug Harmonia axyridis

Kim

Lee

Kwon

et al. 2013

International Journal of Oncology

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Abstract.Harmoniasin is a defensin-like antimicrobial peptide identified from the ladybug Harmonia axyridis. Among the synthetic homodimer peptide analogues derived from harmoniasin, HaA4 has been found to have antibacterial activity without hemolytic activity. In this study, we investigated whether HaA4 has anticancer activity against human leukemia cell lines such as U937 and Jurkat cells. HaA4 manifested cytotoxicity and decreased the cell viability of U937 and Jurkat cells in MTS assay and LDH release assay. We found that HaA4 induced apoptotic and necrotic cell death of the leukemia cells using flow cytometric analysis, acridine orange/ethidium bromide staining and nucleosomal fragmentation of genomic DNA. Activation of caspase-7 and -9 and fragmentation of poly (ADP-ribose) polymerase was detected in the HaA4-treated leukemia cells, suggesting induction of a caspase-dependent apoptosis pathway by HaA4. Caspase-dependent apoptosis was further confirmed by reversal of the HaA4-induced viability reduction by treatment of Z-VAD-FMK, a pan-caspase inhibitor. In conclusion, HaA4 caused necrosis and caspase-dependent apoptosis in both U937 and Jurkat leukemia cells, which suggests potential utility of HaA4 as a cancer therapeutic agent.

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“…Of interest, we found expression of magainin (Cruciani et al, 1992;Baker et al, 1993;Soballe et al, 1995, Matsuzaki, 1998 during embryonic development (Fig. 3I).…”

Section: Expression Of Regulatory Subunitsmentioning

confidence: 57%

Early embryonic expression of ion channels and pumps in chick and Xenopus development

Rutenberg

Cheng²,

Levin³

2002

Developmental Dynamics

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An extensive body of literature implicates endogenous ion currents and standing voltage potential differences in the control of events during embryonic morphogenesis. Although the expression of ion channel and pump genes, which are responsible for ion flux, has been investigated in detail in nervous tissues, little data are available on the distribution and function of specific channels and pumps in early embryogenesis. To provide a necessary basis for the molecular understanding of the role of ion flux in development, we surveyed the expression of ion channel and pump mRNAs, as well as other genes that help to regulate membrane potential. Analysis in two species, chick and Xenopus, shows that several ion channel and pump mRNAs are present in specific and dynamic expression patterns in early embryos, well before the appearance of neurons. Examination of the distribution of maternal mRNAs reveals complex spatiotemporal subcellular localization patterns of transcripts in early blastomeres in Xenopus. Taken together, these data are consistent with an important role for ion flux in early embryonic morphogenesis; this survey characterizes candidate genes and provides information on likely embryonic contexts for their function, setting the stage for functional studies of the morphogenetic roles of ion transport.

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Experimental local therapy of human melanoma with lytic magainin peptides

Cited by 71 publications

References 19 publications

In Vitro Antiplasmodium Effects of Dermaseptin S4 Derivatives

In Vitro Antiplasmodium Effects of Dermaseptin S4 Derivatives

Anticancer activity of a synthetic peptide derived from harmoniasin, an antibacterial peptide from the ladybug Harmonia axyridis

Early embryonic expression of ion channels and pumps in chick and Xenopus development

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