title: Stevia rebaudiana ethanolic extract exerts better antioxidant properties and antiproliferative effects in tumour cells than its diterpene glycoside stevioside.
abstract: Steviol glycosides are currently being used as natural sweeteners by the food industry and Stevia rebaudiana has long been used as a sweet plant in South America for patients suffering from diabetes. In this study, a Stevia rebaudiana ethanolic extract (SREE) was prepared, analysed and tested for antioxidant activity in terms of free radical scavenging properties and antiproliferative effects in cervix (HeLa), pancreatic (MiaPaCa-2) and colonic (HCT116) cancer cells. The antiproliferative mechanism was confirmed by testing the effects on cyclin D1-CDK4. Bioassays were also performed for the diterpene glycoside stevioside. Our results demonstrate that the extract acts as an antioxidant being able to scavenge free radicals, but this activity was not due to stevioside. The extract also induced cell death in the three cell lines, being more active against cervix cancer cells (HeLa); however, the concentration of stevioside needed to produce antiproliferative effects was higher than the amount of steviol glycosides found in a lower dose of extract inducing cell death. In addition, the extract clearly inhibited CDK4 whereas stevioside did not, concluding that the antiproliferative activity of stevia may be due to inhibition of cyclin-dependent kinases performed by other compounds of the extract.
authors.affiliation: Department of Pharmacy, Faculty of Health Sciences, San Jorge University, Villanueva de Gállego (Zaragoza), Spain. ilopez@usj.es.
authors.forename: Víctor
authors.initials: V
authors.lastname: López
authors.affiliation: Department of Pharmacy, Faculty of Health Sciences, San Jorge University, Villanueva de Gállego (Zaragoza), Spain. ilopez@usj.es.
authors.forename: Sergio
authors.initials: S
authors.lastname: Pérez
authors.affiliation: Department of Pharmacy, Faculty of Health Sciences, San Jorge University, Villanueva de Gállego (Zaragoza), Spain. ilopez@usj.es and Institute of Biocomputation and Physics of Complex Systems (BIFI), Joint Unit IQFRCSIC-BIFI, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Arturo
authors.initials: A
authors.lastname: Vinuesa
authors.affiliation: Departamento de Medicina Física y Farmacología, Facultad de Farmacia, Universidad de La Laguna, La Laguna, Tenerife, Spain.
authors.forename: Christian
authors.initials: C
authors.lastname: Zorzetto
authors.affiliation: Institute of Biocomputation and Physics of Complex Systems (BIFI), Joint Unit IQFRCSIC-BIFI, Universidad de Zaragoza, Zaragoza, Spain and Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain and IIS Aragón, Zaragoza, Spain and Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Abian
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D036625:Stevia / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D045786:Diterpenes, Kaurane; D005960:Glucosides; D010936:Plant Extracts; C012043:stevioside