In vitro anticancer studies of a small library of cyclic lipopeptides against the human cervix adenocarcinoma HeLa cells
| Autor: | Hmedat Ali N., Morejón Micjel C., Rivera Daniel G., Pantelić Nebojša Đ., Wessjohann Ludger A., Kaluđerović Goran N. |
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| Jazyk: | angličtina |
| Rok vydání: | 2024 |
| Předmět: | |
| Zdroj: | Journal of the Serbian Chemical Society, Vol 89, Iss 4, Pp 471-484 (2024) |
| Druh dokumentu: | article |
| ISSN: | 0352-5139 1820-7421 24010901 |
| DOI: | 10.2298/JSC240109018H |
| Popis: | Various cyclic lipopeptides (CLPs, 23 compounds) were tested for their antitumor potential against human cervix adenocarcinoma HeLa cells. From the fast screening (tested concentrations: 0.01 and 10 μM) compound 10 ((12S,6S,10S,13S)-6-((R)-sec-butyl)-7-(2-(dodecylamino)-2-oxoethyl)-13-isopropyl- 82-nitro-2,5,12,15-tetraoxo-4,7,11,14-tetraaza-1(1,2)-pyrrolidina-8(1,4)-benzenacyclopentadecaphane- 10-carboxamide) was identified as active against HeLa cell line. The MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and CV (crystal violet) assays revealed at least five times higher cytotoxic potential of 10 (IC50 = 12.3±1.8 μM, MTT; 9.4±1.5 μM; CV) in comparison to control drug natural occurring CLP surfactin (IC50 = 64.9±0.8 μM, MTT; 76.2±1.6 μM; CV). The cell cycle analysis performed by DAPI (4',6-diamidino- 2-phenylindole) assay indicated the involvement of apoptosis in HeLa cell death upon treatment with 10, which was confirmed by apoptosis assay (annexin V/PI). Furthermore, during this process caspase activation could be detected (ApoStat assay, immunocytochemistry caspase-3 analysis). The flow cytometry analysis did not display induction of autophagy as a possible death mechanism in HeLa cells upon 10 treatment. The current findings could be used to design more effective CLPs based on 10 structure as potential anticancer agents. |
| Databáze: | Directory of Open Access Journals |
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