Withania somnifera Induces Cytotoxic and Cytostatic Effects on Human T Leukemia Cells.

Eleonora Turrini, Cinzia Calcabrini, Piero Sestili, Elena Catanzaro, Elena de Gianni, Anna Rita Diaz, Patrizia Hrelia, Massimo Tacchini, Alessandra Guerrini, Barbara Canonico, Stefano Papa, Giovanni Valdrè, Carmela Fimognari

Journal: Toxins 2017;8(5):147

PMID: 27187469

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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.

Address: Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy. [email protected].; Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy. [email protected].; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via Saffi 2, 61029 Urbino, Italy. [email protected].; Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy. [email protected].; Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy. [email protected].; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via Saffi 2, 61029 Urbino, Italy. [email protected].; Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via Irnerio 48, 40126 Bologna, Italy. [email protected].; Department of Life Sciences and Biotechnology (SVeB)-LT Terra & Acqua Tech RU, University of Ferrara, Corso Ercole I d'Este 32, I-44121 Ferrara, Italy. [email protected].; Department of Life Sciences and Biotechnology (SVeB)-LT Terra & Acqua Tech RU, University of Ferrara, Corso Ercole I d'Este 32, I-44121 Ferrara, Italy. [email protected].; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via Saffi 2, 61029 Urbino, Italy. [email protected].; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via Saffi 2, 61029 Urbino, Italy. [email protected].; Department of Biological, Geological and Environmental Sciences (BiGeA), Alma Mater Studiorum-University of Bologna, Piazza di Porta S. Donato 1, 40126 Bologna, Italy. [email protected].; Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy. [email protected].

DOI: 10.3390/toxins8050147

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https://assays.cancer.gov/CPTAC-177

MeSH Terms: Adenosine Triphosphate, Antineoplastic Agents, Apoptosis, Calcium, Calreticulin, DNA Damage, HSP70 Heat-Shock Proteins, HSP90 Heat-Shock Proteins, Humans, Jurkat Cells, Leukemia, T-Cell, Mutagens, Oxidative Stress, Plant Extracts, Plant Roots, Withania