title: Antiproliferative Effects of Cynara cardunculus L. var. altilis (DC) Lipophilic Extracts.
abstract: Besides being traditionally used to relieve hepatobiliary disorders,Cynara cardunculusL. has evidenced anticancer potential on triple-negative breast cancer (TNBC). This study highlights the antiproliferative effects of lipophilic extracts fromC. cardunculusL. var.altilis(DC) leaves and florets, and of their major compounds, namely cynaropicrin and taraxasteryl acetate, against MDA-MB-231 cells. Our results demonstrated that MDA-MB-231 cells were much less resistant to leaves extract (IC5010.39 µg/mL) than to florets extract (IC50315.22 µg/mL), during 48 h. Moreover, leaves extract and cynaropicrin (IC506.19 µg/mL) suppressed MDA-MB-231 cells colonies formation, via an anchorage-independent growth assay. Leaves extract and cynaropicrin were also assessed regarding their regulation on caspase-3 activity, by using a spectrophotometric assay, and expression levels of G2/mitosis checkpoint and Akt signaling pathway proteins, by Western blotting. Leaves extract increased caspase-3 activity, while cynaropicrin did not affect it. Additionally, they caused p21Waf1/Cip1upregulation, as well as cyclin B1 and phospho(Tyr15)-CDK1 accumulation, which may be related to G2 cell cycle arrest. They also downregulated phospho(Ser473)-Akt, without changing total Akt1 level. Cynaropicrin probably contributed to leaves extract antiproliferative action. These promising insights suggest that cultivated cardoon leaves lipophilic extract and cynaropicrin may be considered toward a natural-based therapeutic approach on TNBC.
authors.affiliation: Centro de Biotecnologia Agrícola e Agro-Alimentar do Alentejo (CEBAL)/Instituto Politécnico de Beja (IPBeja), 7801-908 Beja, Portugal. patricia.ramos@cebal.pt.|CICECO and Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal. patricia.ramos@cebal.pt.
authors.forename: Patrícia A B
authors.initials: PA
authors.lastname: Ramos
authors.affiliation: Centro de Biotecnologia Agrícola e Agro-Alimentar do Alentejo (CEBAL)/Instituto Politécnico de Beja (IPBeja), 7801-908 Beja, Portugal. angela.guerra@cebal.pt.|CICECO and Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal. angela.guerra@cebal.pt.
authors.forename: Ângela R
authors.initials: ÂR
authors.lastname: Guerra
authors.affiliation: Centro de Biotecnologia Agrícola e Agro-Alimentar do Alentejo (CEBAL)/Instituto Politécnico de Beja (IPBeja), 7801-908 Beja, Portugal. olinda.guerreiro@cebal.pt.|CIISA, Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, ULisboa, Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal. olinda.guerreiro@cebal.pt.
authors.forename: Olinda
authors.initials: O
authors.lastname: Guerreiro
authors.affiliation: CICECO and Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal. santos.sonia@ua.pt.
authors.forename: Sónia A O
authors.initials: SA
authors.lastname: Santos
authors.affiliation: CESAM and Department of Biology, University of Aveiro, 3810-193 Aveiro, Portugal. holiveira@ua.pt.
authors.forename: Helena
authors.initials: H
authors.lastname: Oliveira
authors.affiliation: CICECO and Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal. cfreire@ua.pt.
authors.forename: Carmen S R
authors.initials: CS
authors.lastname: Freire
authors.affiliation: CICECO and Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal. armsil@ua.pt.
authors.forename: Armando J D
authors.initials: AJ
authors.lastname: Silvestre
authors.affiliation: Centro de Biotecnologia Agrícola e Agro-Alimentar do Alentejo (CEBAL)/Instituto Politécnico de Beja (IPBeja), 7801-908 Beja, Portugal. fatima.duarte@cebal.pt.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Duarte
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D031942:Cynara / Q000737:chemistry*; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D007783:Lactones; D010936:Plant Extracts; D012717:Sesquiterpenes; D051057:Proto-Oncogene Proteins c-akt; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; C075687:cynaropicrin
keywords: Cynara cardunculus L. var. altilis (DC); cynaropicrin; lipophilic extracts; p21Waf1/Cip1 upregulation; phospho(Ser473)-Akt downregulation; phospho(Tyr15)-CDK1 protein accumulation; taraxasteryl acetate; triple-negative breast cancer MDA-MB-231 cell line