Studies of the antitumor mechanism of action of dermaseptin B2, a multifunctional cationic antimicrobial peptide, reveal a partial implication of cell surface glycosaminoglycans
| Autor: | Mohamed Amiche, Patricia Zadigue, Jean Delbé, Loussiné Zargarian, Clara Newton, Yamina Hamma-Kourbali, Mickael Miro-Padovani, Karen Le Saux, Meriem Mazouni, Célia Dos Santos, Sabah Hamadat |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Confocal Microscopy Luminescence Cell Cell Membranes Cancer Treatment lcsh:Medicine Cell membrane purl.org/becyt/ford/1 [https] 0302 clinical medicine Neoplasms Medicine and Health Sciences lcsh:Science Glycosaminoglycans Staining Microscopy Multidisciplinary Chemistry Sulfates Physics Electromagnetic Radiation Cell Staining Chemical Synthesis Light Microscopy Crystal Violet Staining DERMASEPTIN B2 medicine.anatomical_structure Biochemistry Oncology 030220 oncology & carcinogenesis Physical Sciences medicine.symptom Cellular Structures and Organelles Anura CIENCIAS NATURALES Y EXACTAS Research Article Biosynthetic Techniques Otras Ciencias Biológicas Antineoplastic Agents Research and Analysis Methods behavioral disciplines and activities Fluorescence Amphibian Proteins Ciencias Biológicas 03 medical and health sciences Structure-Activity Relationship Cell Line Tumor mental disorders medicine Animals Humans Secretion Amino Acid Sequence purl.org/becyt/ford/1.6 [https] Peptide Synthesis Cell Proliferation GLYCOSAMINOGLYCANS Dermaseptin lcsh:R Chemical Compounds Biology and Life Sciences Cell Biology ANTITUMORAL ACTIVITY In vitro eye diseases 030104 developmental biology Mechanism of action Cell culture Cytoplasm Specimen Preparation and Treatment Salts lcsh:Q Antimicrobial Cationic Peptides |
| Zdroj: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET PLoS ONE, Vol 12, Iss 8, p e0182926 (2017) PLoS ONE |
| DOI: | 10.1371/journal.pone.0182926 |
| Popis: | Dermaseptin-B2 (DRS-B2) is a multifunctional cationic antimicrobial peptide (CAP) isolated from frog skin secretion. We previously reported that DRS-B2 possesses anticancer and antiangiogenic activities in vitro and in vivo. In the present study, we evaluated the antiproliferative activity of DRS-B2 on numerous tumor cell lines, its cell internalization and studies of its molecular partners as well as their influences on its structure. Confocal microscopy using ([Alexa594]-(Cys0)-DRS-B2) shows that in sensitive human tumor cells (PC3), DRS-B2 seems to accumulate rapidly at the cytoplasmic membranes and enters the cytoplasm and the nucleus, while in less sensitive tumor cells (U87MG), DRS-B2 is found packed in vesicles at the cell membrane. Furthermore FACS analysis shows that PC3 cells viability decreases after DRS-B2 treatment while U87 MG seems to be unaffected. However, "pull down" experiments performed with total protein pools from PC3 or U87MG cells and the comparison between the antiproliferative effect of DRS-B2 and its synthetic analog containing all Damino acids suggest the absence of a stereo-selective protein receptor. Pretreatment of PC3 cells with sodium chlorate, decreases the antiproliferative activity of DRS-B2. This activity is partially restored after addition of exogenous chondroitin sulfate C (CS-C). Moreover, we demonstrate that at nanomolar concentrations CS-C potentiates the antiproliferative effect of DRS-B2. These results highlight the partial implication of glycosaminoglycans in the mechanism of antiproliferative action of DRS-B2. Structural analysis of DRS-B2 by circular dichroism in the presence of increasing concentration of CS-C shows that DRS-B2 adopts anα-helical structure. Finally, structure-activity-relationship studies suggest a key role of the W residue in position 3 of the DRS-B2 sequence for its antiproliferative activity. Fil: Dos Santos, Célia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centre National de la Recherche Scientifique; Francia Fil: Hamadat, Sabah. Centre National de la Recherche Scientifique; Francia. University Paris Est Creteil; Francia Fil: Le Saux, Karen. University Paris Est Creteil; Francia Fil: Newton, Clara. Centre National de la Recherche Scientifique; Francia. University Paris Est Creteil; Francia Fil: Mazouni, Meriem. Centre National de la Recherche Scientifique; Francia. University Paris Est Creteil; Francia Fil: Zargarian, Loussiné. Centre National de la Recherche Scientifique; Francia Fil: Miro-Padovani, Mickael. University Paris Est Creteil; Francia Fil: Zadigue, Patricia. University Paris Est Creteil; Francia Fil: Delbé, Jean. University Paris Est Creteil; Francia Fil: Hamma-Kourbali, Yamina. University Paris Est Creteil; Francia Fil: Amiche, Mohamed. University Paris Est Creteil; Francia |
| Databáze: | OpenAIRE |
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