title: Cytotoxic activity and antioxidant capacity of purified lichen metabolites: an in vitro study.
abstract: The purpose of this study was to investigate the effects of six lichen metabolites (diffractaic acid, lobaric acid, usnic acid, vicanicin, variolaric acid, protolichesterinic acid) on proliferation, viability and reactive oxygen species (ROS) level towards three human cancer cell lines, MCF-7 (breast adenocarcinoma), HeLa (cervix adenocarcinoma) and HCT-116 (colon carcinoma). Cells were treated with different concentrations (2.5-100 μM) of these compounds for 48 h. In this comparative study, our lichen metabolites showed various cytotoxic effects in a concentration-dependent manner, and usnic acid was the most potent cytotoxic agent, while variolaric acid did not inhibit the proliferation of any of the three cell lines used. All tested lichen compounds did not exhibit free radical scavenging activity using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The lichen metabolites did not significantly increase the intracellular ROS level and did not prevent oxidative injury induced by t-butylhydroperoxide in HeLa cells. To better clarify the mechanism(s) of cytotoxic effect induced by protolichesterinic acid in HeLa cells, we investigated apoptotic markers such as condensation and fragmentation of nuclear chromatin and activation of caspase-3, 8 and 9. Our results revealed that the antiproliferative activity of 40 μM protolichesterinic acid in HeLa cells is related to its ability to induce programmed cell death involving caspase-3, 8 and 9 activation.
authors.affiliation: Department of Biomedical Sciences and Technologies, University of L'Aquila, Via Vetoio, Coppito 2, 67100, L' Aquila, Italy. fabrizia.brisdelli@cc.univaq.it
authors.forename: Fabrizia
authors.initials: F
authors.lastname: Brisdelli
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Perilli
authors.forename: Doriana
authors.initials: D
authors.lastname: Sellitri
authors.forename: Marisa
authors.initials: M
authors.lastname: Piovano
authors.forename: Juan A
authors.initials: JA
authors.lastname: Garbarino
authors.forename: Marcello
authors.initials: M
authors.lastname: Nicoletti
authors.forename: Argante
authors.initials: A
authors.lastname: Bozzi
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Amicosante
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Celenza
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D000840:Anisoles / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001572:Benzofurans / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D053630:Depsides / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D062385:Hydroxybenzoates / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology; D008011:Lichens / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012459:Salicylates / Q000494:pharmacology
chemical_list: D000840:Anisoles; D000975:Antioxidants; D001572:Benzofurans; D053630:Depsides; D016166:Free Radical Scavengers; D062385:Hydroxybenzoates; D007783:Lactones; D017382:Reactive Oxygen Species; D012459:Salicylates; C570018:vicanicin; C073339:usnic acid; C095781:protolichesterinic acid; C093528:diffractaic acid; C104417:lobaric acid; D020169:Caspases; D015107:4-Butyrolactone