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 ?M) 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 ?M, MTT; 9.4
? 1.5 ?M; CV) in comparison to control drug natural occurring CLP surfactin
(IC50 = 64.9 ? 0.8 ?M, MTT; 76.2 ? 1.6 ?M; 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.