title: Withania somnifera Induces Cytotoxic and Cytostatic Effects on Human T Leukemia Cells.
abstract: Cancer chemotherapy is characterized by an elevated intrinsic toxicity and the development of drug resistance. Thus, there is a compelling need for new intervention strategies with an improved therapeutic profile. Immunogenic cell death (ICD) represents an innovative anticancer strategy where dying cancer cells release damage-associated molecular patterns promoting tumor-specific immune responses. The roots of Withania somnifera (W. somnifera) are used in the Indian traditional medicine for their anti-inflammatory, immunomodulating, neuroprotective, and anticancer activities. The present study is designed to explore the antileukemic activity of the dimethyl sulfoxide extract obtained from the roots of W. somnifera (WE). We studied its cytostatic and cytotoxic activity, its ability to induce ICD, and its genotoxic potential on a human T-lymphoblastoid cell line by using different flow cytometric assays. Our results show that WE has a significant cytotoxic and cytostatic potential, and induces ICD. Its proapoptotic mechanism involves intracellular Ca(2+) accumulation and the generation of reactive oxygen species. In our experimental conditions, the extract possesses a genotoxic potential. Since the use of Withania is suggested in different contexts including anti-infertility and osteoarthritis care, its genotoxicity should be carefully considered for an accurate assessment of its risk-benefit profile.
authors.affiliation: Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy. eleonora.turrini@unibo.it.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Turrini
authors.affiliation: Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy. cinzia.calcabrini@unibo.it.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Calcabrini
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via Saffi 2, 61029 Urbino, Italy. piero.sestili@uniurb.it.
authors.forename: Piero
authors.initials: P
authors.lastname: Sestili
authors.affiliation: Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy. elena.catanzaro2@unibo.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Catanzaro
authors.affiliation: Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy. elena.degianni2@unibo.it.
authors.forename: Elena
authors.initials: E
authors.lastname: de Gianni
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via Saffi 2, 61029 Urbino, Italy. anna.diaz@uniurb.it.
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Diaz
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via Irnerio 48, 40126 Bologna, Italy. patrizia.hrelia@unibo.it.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Hrelia
authors.affiliation: Department of Life Sciences and Biotechnology (SVeB)-LT Terra &amp; Acqua Tech RU, University of Ferrara, Corso Ercole I d'Este 32, I-44121 Ferrara, Italy. massimo.tacchini@unife.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Tacchini
authors.affiliation: Department of Life Sciences and Biotechnology (SVeB)-LT Terra &amp; Acqua Tech RU, University of Ferrara, Corso Ercole I d'Este 32, I-44121 Ferrara, Italy. grrlsn@unife.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Guerrini
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via Saffi 2, 61029 Urbino, Italy. barbara.canonico@uniurb.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Canonico
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via Saffi 2, 61029 Urbino, Italy. stefano.papa@uniurb.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Papa
authors.affiliation: Department of Biological, Geological and Environmental Sciences (BiGeA), Alma Mater Studiorum-University of Bologna, Piazza di Porta S. Donato 1, 40126 Bologna, Italy. giovanni.valdre@unibo.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Valdrè
authors.affiliation: Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy. carmela.fimognari@unibo.it.
authors.forename: Carmela
authors.initials: C
authors.lastname: Fimognari
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D037282:Calreticulin / Q000378:metabolism; D004249:DNA Damage; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D015458:Leukemia, T-Cell; D009153:Mutagens / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots; D032341:Withania
chemical_list: D000970:Antineoplastic Agents; D037282:Calreticulin; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D009153:Mutagens; D010936:Plant Extracts; D000255:Adenosine Triphosphate; D002118:Calcium
keywords: Withania somnifera; apoptosis; cell cycle; genotoxicity; immunogenic cell death; leukemia; oxidative stress