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Lung Cancer Chemopreventive Activity of Patulin Isolated from Penicillium vulpinum

Gindro, Katia
Published in Molecules. 2018, vol. 23, no. 3
Abstract Lung cancer is the most lethal form of cancer in the world. Its development often involves an overactivation of the nuclear factor kappa B (NF-κB) pathway, leading to increased cell proliferation, survival, mobility, and a decrease in apoptosis. Therefore, NF-κB inhibitors are actively sought after for both cancer chemoprevention and therapy, and fungi represent an interesting unexplored reservoir for such molecules. The aim of the present work was to find naturally occurring lung cancer chemopreventive compounds by investigating the metabolites of Penicillium vulpinum, a fungus that grows naturally on dung. Penicillium vulpinum was cultivated in Potato Dextrose Broth and extracted with ethyl acetate. Bioassay-guided fractionation of this extract was performed by measuring NF-κB activity using a HEK293 cell line transfected with an NF-κB-driven luciferase reporter gene. The mycotoxin patulin was identified as a nanomolar inhibitor of TNF-α-induced NF-κB activity. Immunocytochemistry and Western blot analyses revealed that its mechanism of action involved an inhibition of p65 nuclear translocation and was independent from the NF-κB inhibitor α (IκBα) degradation process. Enhancing its interest in lung cancer chemoprevention, patulin also exhibited antiproliferative, proapoptotic, and antimigration effects on human lung adenocarcinoma cells through inhibition of the Wnt pathway.
Keywords A549 CellsAntineoplastic Agents/chemistry/isolation & purification/pharmacologyCell Proliferation/drug effectsCell Survival/drug effectsDown-RegulationDrug Screening Assays, AntitumorGene Expression Regulation, Neoplastic/drug effectsHEK293 CellsHumansLung Neoplasms/drug therapy/metabolismPatulin/chemistry/isolation & purification/pharmacologyPenicillium/chemistrySignal Transduction/drug effectsTranscription Factor RelA/metabolismTumor Necrosis Factor-alpha/metabolism
PMID: 29534536
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Article (Published version) (2.4 MB) - public document Free access
Research groups Pharmacognosie
Phytochimie et produits naturels bioactifs
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MONTEILLIER, Aymeric et al. Lung Cancer Chemopreventive Activity of Patulin Isolated from Penicillium vulpinum. In: Molecules, 2018, vol. 23, n° 3. doi: 10.3390/molecules23030636 https://archive-ouverte.unige.ch/unige:108169

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Deposited on : 2018-09-21

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