ArticleNaunyn-Schmiedeberg's archives of pharmacology2025
Molecular docking and antitumor evaluation of liposomal nanoformulations containing citrinin.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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17 authors.
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Abstract
The search for novel drugs based on natural products combined with nanosystems has circumvented limitations and barriers in cancer treatment. Citrinin (CIT), a mycotoxin produced by the fungus Penicillium citrinum, has demonstrated cytotoxicity in tumor models and may represent a promising antitumor agent. In this study, we aimed to evaluate the cytotoxic, genotoxic, and mutagenic effects of CIT and a liposomal nanoformulation containing CIT (LP-CIT) in MCF7 breast cancer cells. The selected concentrations were based on preliminary range-finding assays to determine optimal cytotoxicity while maintaining assay reliability. The toxicogenetic evaluations and mechanistic analyses included MTT, trypan blue exclusion, cytokinesis-block micronucleus (CBMN) assays, fluorescence confocal microscopy, and molecular docking studies. CIT and LP-CIT showed cytotoxicity in MCF7 cells, with LP-CIT presenting significantly reduced IC50 values (0.90 µg/mL) compared to free CIT (18.25 µg/mL), possibly due to enhanced cellular uptake via liposomal delivery. Confocal microscopy revealed that both treatments significantly reduced cell viability and increased apoptosis. In addition, CBMN assays demonstrated equivalent cytostatic and mutagenic effects for CIT and LP-CIT. Docking analysis suggested interactions of CIT with mitogen-activated protein kinases, including MAPK-1, B-Raf, and ERK, indicating possible activation of apoptotic pathways via ERK1/2. In conclusion, CIT and its liposomal nanoformulation (LP-CIT) exhibited cytotoxic and mutagenic activity in human breast tumor cells by inducing apoptosis and modulating oncogenic pathways.
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