El Gaafary M.Ezzat, Shahira MEl Sayed A.M.Sabry O.M.Hafner S.Lang S.Schmiech M.Syrovets T.Simmet T.Department of PharmacognosyCollege of PharmacyCairo UniversityGiza11562Egypt; Pharmacognosy DepartmentFaculty of PharmacyOctober University for Modern Sciences and Arts (MSA)Cairo11562Egypt; Institute of Pharmacology of Natural Products and Clinical PharmacologyUlm UniversityUlmD-89081Germany2020-01-092020-01-0920171633864https://doi.org/10.1021/acs.jnatprod.7b00546PubMed ID 29190084https://t.ly/LXMeGScopusWe investigated the cytotoxic potential of the cardenolide glycoside acovenoside A against non-small-cell lung cancer cells. Lung cancer is the leading cause of cancer-related mortality and the second most common cancer diagnosed. Epidemiological studies revealed a direct correlation between the regular administration of cardiac glycosides and a lower incidence of various cancers. Acovenoside A, isolated from the pericarps of Acokanthera oppositifolia, potently inhibited proliferation and induced cytotoxicity in A549 non-small-cell lung cancer cells with an IC 50 of 68 � 3 nM after 48 h of exposure. Compared to the antineoplastic agent doxorubicin, acovenoside A was more potent in inhibiting the viability of A549 cancer cells. Moreover, acovenoside A exhibited selectivity against cancer cells, being significantly less toxic to lung fibroblasts and nontoxic for peripheral blood mononuclear cells. Analysis of the cell cycle profile in acovenoside A-treated A549 cells revealed mitotic arrest, due to accumulation of the G 2 /M regulators cyclin B 1 and CDK1, and cytokinesis failure. Furthermore, acovenoside A affected the mitochondrial membrane integrity and induced production of radical oxygen species, which resulted in induction of canonical apoptosis, manifested by caspase 3 activation and DNA fragmentation. Based on our results, acovenoside A warrants further exploration as a potential anticancer lead. � 2017 The American Chemical Society and American Society of Pharmacognosy.EnglishOctober University for Modern Sciences and Artsجامعة أكتوبر للعلوم الحديثة والآدابUniversity of Modern Sciences and ArtsMSA Universityacovenoside acardenolidecaspase 3cyclin B1cyclin dependent kinase 1cytotoxic agentdoxorubicinebselennorphenazoneprotein p53reactive oxygen metabolitetempolunclassified drugacovenoside Aantineoplastic agentcardenolidedoxorubicinreactive oxygen metaboliteAcokanthera oppositifoliaapoptosisArticlecell cyclecell cycle progressioncell proliferationcell viabilitycontrolled studycytokinesiscytotoxicityDNA fragmentationdrug mechanismdrug sensitivityfluorescenceG2 phase cell cycle checkpointhumanhuman cellIC50lung fibroblastlung non-small cell carcinoma cell lineM phase cell cycle checkpointmitochondrial membrane potentialmitosismitosis inhibitionnon small cell lung canceroxidative stresspericarpperipheral blood mononuclear cellprotein phosphorylationshrubA-549 cell lineapoptosiscell survivaldrug effectepidemiologyfibroblastlung tumormetabolismmitochondrial membranemitosismononuclear cellnon small cell lung cancertumor cell lineA549 CellsAntineoplastic AgentsApoptosisCarcinoma, Non-Small-Cell LungCardenolidesCell Line, TumorCell ProliferationCell SurvivalDNA FragmentationDoxorubicinEpidemiologic StudiesFibroblastsG2 Phase Cell Cycle CheckpointsHumansLeukocytes, MononuclearLung NeoplasmsMitochondrial MembranesMitosisReactive Oxygen SpeciesArticlehttps://doi.org/10.1021/acs.jnatprod.7b00546PubMed ID 29190084