The IPB has once again been recognized for its exemplary actions in terms of equal opportunity-oriented personnel and organizational policies and has received the TOTAL E-QUALITY certification for the…
The Plant Science Student Conference (PSSC) has been organised by students from the two Leibniz institutes, IPK and IPB, every year for the last 20 years. In this interview, Christina Wäsch (IPK) and…
Hmedat, A. N.; Morejon, M. C.; Rivera, D. G.; Pantelić, N. ?.; Wessjohann, L. A.; Kaluđerović, G. N.;Cyclic lipopeptides as selective anticancer agents: In vitro efficacy on B16F10 mouse melanoma cellsAnti-Cancer Agents Med. Chem.25873-882(2025)DOI: 10.2174/0118715206351208250102114944
Objective:
In this study, 25 synthetic cyclic lipopeptides (CLPs) were investigated for their anticancer
potential against mouse melanoma (B16F10) cells, human prostate cancer (PC-3), human colorectal adenocarcinoma
(HT-29) and mouse embryonic fibroblast (NIH3T3) cells.
Methods:
The cytotoxic activity of investigated compounds was evaluated using MTT and CV assays. In order to
examine the mechanism of action of the most potent compound cell cycle analysis, apoptosis assay, caspase activity,
CFSE and DHR staining, DAF-FM, autophagy and immunocytochemistry caspase-3 assays were performed.
Results:
During the fast screening, compound 9, was identified as prospective active CLP against B16F10 cell
line at 10 μM concentration. MTT and CV assays exhibited at least four times higher cytotoxic potential of 9
(IC50 = 8.4±1.3 μM, MTT; 10.6±1.1 μM, CV) in comparison to control drug natural occurring CLP surfactin
(IC50 = 50.3±0.6 μM, MTT; 40.4±0.3 μM, CV). The use of flow cytometry analysis confirmed that apoptosis
was involved in the death of B16F10 cells after treatment with 9, as demonstrated also by DAPI staining. Caspase
activity could be detected during cell death (ApoStat assay, immunocytochemistry caspase-3 assay). Compound 9
provokes enhancement of nitric oxide (NO) production in B16F10 cells but does not trigger ROS/RNS generation
or autophagy.
Conclusion:
The study highlights synthetic compound 9 superior tumor-specificity and potential as an anticancer
agent compared to surfactin and cisplatin. These findings could guide the development of more selective and less
harmful macrocyclic lipopeptides for cancer therapy.