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Toxins (Basel). 2016 May 12;8(5). pii: E147. doi: 10.3390/toxins8050147.

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

Author information

1
Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy. eleonora.turrini@unibo.it.
2
Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy. cinzia.calcabrini@unibo.it.
3
Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via Saffi 2, 61029 Urbino, Italy. piero.sestili@uniurb.it.
4
Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy. elena.catanzaro2@unibo.it.
5
Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy. elena.degianni2@unibo.it.
6
Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via Saffi 2, 61029 Urbino, Italy. anna.diaz@uniurb.it.
7
Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via Irnerio 48, 40126 Bologna, Italy. patrizia.hrelia@unibo.it.
8
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. massimo.tacchini@unife.it.
9
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. grrlsn@unife.it.
10
Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via Saffi 2, 61029 Urbino, Italy. barbara.canonico@uniurb.it.
11
Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via Saffi 2, 61029 Urbino, Italy. stefano.papa@uniurb.it.
12
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.
13
Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy. carmela.fimognari@unibo.it.

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.

KEYWORDS:

Withania somnifera; apoptosis; cell cycle; genotoxicity; immunogenic cell death; leukemia; oxidative stress

PMID:
27187469
PMCID:
PMC4885062
DOI:
10.3390/toxins8050147
[Indexed for MEDLINE]
Free PMC Article

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