Mitoparan and target-selective chimeric analogues: Membrane translocation and intracellular redistribution induces mitochondrial apoptosis

Jones, Sarah; Martel, Cécile; Belzacq-Casagrande, Anne-Sophie; Brenner, Catherine; Howl, John

doi:10.1016/j.bbamcr.2008.01.009

Cited by 52 publications

(108 citation statements)

References 33 publications

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“…Similar effects were induced by melittin [175], mastoparan [176] and its analogs [177], and spider venom peptide lycosin-1 [178]. Being internalized, these peptides interfere with cell signaling pathways by attenuating the activity of the key proteins.…”

Section: Anticancer Potentialmentioning

confidence: 60%

Latarcins: versatile spider venom peptides

Dubovskii

Vassilevski

Kozlov

et al. 2015

Cell. Mol. Life Sci.

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Arthropod venoms feature the presence of cytolytic peptides believed to act synergetically with neurotoxins to paralyze prey or deter aggressors. Many of them are linear, i.e., lack disulfide bonds. When isolated from the venom, or obtained by other means, these peptides exhibit common properties. They are cationic; being mostly disordered in aqueous solution, assume amphiphilic α-helical structure in contact with lipid membranes; and exhibit general cytotoxicity, including antifungal, antimicrobial, hemolytic, and anticancer activities. To suit the pharmacological needs, the activity spectrum of these peptides should be modified by rational engineering. As an example, we provide a detailed review on latarcins (Ltc), linear cytolytic peptides from Lachesana tarabaevi spider venom. Diverse experimental and computational techniques were used to investigate the spatial structure of Ltc in membrane-mimicking environments and their effects on model lipid bilayers. The antibacterial activity of Ltc was studied against a panel of Gram-negative and Gram-positive bacteria. In addition, the action of Ltc on erythrocytes and cancer cells was investigated in detail with confocal laser scanning microscopy. In the present review, we give a critical account of the progress in the research of Ltc. We explore the relationship between Ltc structure and their biological activity and derive molecular characteristics, which can be used for optimization of other linear peptides. Current applications of Ltc and prospective use of similar membrane-active peptides are outlined.

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Section: Anticancer Potentialmentioning

confidence: 60%

Latarcins: versatile spider venom peptides

Dubovskii

Vassilevski

Kozlov

et al. 2015

Cell. Mol. Life Sci.

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“…All quantitative co-localization analyses were performed using the Carl Zeiss analysis software incorporating an interactive scatter plot and data table linked to the images [22]. Data were collected from 4 entire images and from 3 independent experiments.…”

Section: Live Cell Scanning Confocal Microscopymentioning

confidence: 99%

“…As indicated in Table 1, we compared common CPP vectors (Tat [5], penetratin [4], C105Y [19] and transportan 10 (TP10; [20])); mast cell secretagogues mastoparan (MP; [21]) and mitoparan (MitP; [22]); human cytochrome c-derived sequences (Cyt c [5][6][7][8][9][10][11][12][13] and Cyt c 77-101 [23]); the anti-angiogenic bioportide nosangiotide [6]; camptide [6], a known activator of G-proteins; and polycationic sequences within the primary structure of leucine rich repeat kinase 2 (LRRK2 1322-1340 and LRRK2 2413-2427 ). The sequences and sources of these peptides are provided in Table 1 and the references therein.…”

Section: Chemical Diversity Of Cpps and Bioportidesmentioning

confidence: 99%

Cell penetrating peptide-mediated transport enables the regulated secretion of accumulated cargoes from mast cells

Howl

Jones

2015

Journal of Controlled Release

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The in vivo utility of technologies employing cell penetrating peptides and bioportides may be compromised by the general capacity of polycationic peptides to activate mast cell secretion. Moreover, the same technologies could be exploited in a clinical setting either to directly modulate intrinsic exocytotic mechanisms or to load mast cells with bioactive cargoes. Comparative investigations identified two cell penetrating vectors, Tat and C105Y, which readily translocate into mast cells without inducing receptor-independent exocytosis. Efficient Tat transduction also enabled the intracellular delivery and accumulation of cargoes within discrete intracellular compartments. A tetramethylrhodamine-Tat conjugate is effectively translocated into the secretory lysosomes of RBL-2H3 cells. In contract, the intracellular delivery of avidin, as a non-covalent complex with a biotinylated Tat vector, is also efficient but the protein is predominantly accumulated outside of secretory lysosomes. Significantly, both cargoes can be subsequently released following mast cell stimulation either by mastoparan, a wasp venom secretagogue, or by the physiological mechanism of antigen-induced aggregation of high affinity IgE receptors. These studies indicate that mast cells could be exploited to direct the delivery of bioactive agents to disease sites as an innovative cell-mediated therapy.

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“…Data on in vivo anti-tumor activities are available for all these compounds (Fulda et al, 2010). Mitochondria-penetrating peptides, such as mastoparan-like sequences, peptides of the innate immunity systems, or the molecules developed by Kelley's group (e.g., Risso et al, 2002; Jones et al, 2008; Horton et al, 2012) also induce MPT. Some MPTP-targeting molecules such as 4-(N-(S-glutathionylacetyl) amino) phenylarsenoxide are currently being evaluated in clinical trials for cancer treatment of refractory tumors (Brenner and Moulin, 2012; Elliott et al, 2012).…”

Section: Mitochondriamentioning

confidence: 99%

Intracellular ion channels and cancer

Leanza¹,

Biasutto²,

Managò³

et al. 2013

Front. Physiol.

122

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Several types of channels play a role in the maintenance of ion homeostasis in subcellular organelles including endoplasmatic reticulum, nucleus, lysosome, endosome, and mitochondria. Here we give a brief overview of the contribution of various mitochondrial and other organellar channels to cancer cell proliferation or death. Much attention is focused on channels involved in intracellular calcium signaling and on ion fluxes in the ATP-producing organelle mitochondria. Mitochondrial K+ channels (Ca2+-dependent BKCa and IKCa, ATP-dependent KATP, Kv1.3, two-pore TWIK-related Acid-Sensitive K+ channel-3 (TASK-3)), Ca2+ uniporter MCU, Mg2+-permeable Mrs2, anion channels (voltage-dependent chloride channel VDAC, intracellular chloride channel CLIC) and the Permeability Transition Pore (MPTP) contribute importantly to the regulation of function in this organelle. Since mitochondria play a central role in apoptosis, modulation of their ion channels by pharmacological means may lead to death of cancer cells. The nuclear potassium channel Kv10.1 and the nuclear chloride channel CLIC4 as well as the endoplasmatic reticulum (ER)-located inositol 1,4,5-trisphosphate (IP3) receptor, the ER-located Ca2+ depletion sensor STIM1 (stromal interaction molecule 1), a component of the store-operated Ca2+ channel and the ER-resident TRPM8 are also mentioned. Furthermore, pharmacological tools affecting organellar channels and modulating cancer cell survival are discussed. The channels described in this review are summarized on Figure 1. Overall, the view is emerging that intracellular ion channels may represent a promising target for cancer treatment.

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Mitoparan and target-selective chimeric analogues: Membrane translocation and intracellular redistribution induces mitochondrial apoptosis

Cited by 52 publications

References 33 publications

Latarcins: versatile spider venom peptides

Latarcins: versatile spider venom peptides

Cell penetrating peptide-mediated transport enables the regulated secretion of accumulated cargoes from mast cells

Intracellular ion channels and cancer

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