An anthocyanin rich strawberry extract induces apoptosis and ROS while decreases glycolysis and fibrosis in human uterine leiomyoma cells

Abstract

// Md Soriful Islam 1, 2, * , Francesca Giampieri 3, * , Milijana Janjusevic 1 , Massimiliano Gasparrini 3 , Tamara Y. Forbes-Hernandez 3 , Luca Mazzoni 3 , Stefania Greco 1 , Stefano Raffaele Giannubilo 3 , Andrea Ciavattini 3 , Bruno Mezzetti 4 , Franco Capocasa 4 , Mario Castellucci 1 , Maurizio Battino 3 , Pasquapina Ciarmela 1, 5 1 Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, Ancona, Italy 2 Biotechnology and Microbiology Laboratory, Department of Botany, University of Rajshahi, Rajshahi, Bangladesh 3 Department of Clinical Science, Università Politecnica delle Marche, Ancona, Italy 4 Department of Agricultural, Food and Environmental Sciences, Università Politecnica delle Marche, Ancona, Italy 5 Department of Information Engineering, Università Politecnica delle Marche, Ancona, Italy * These authors have contributed equally to this work Correspondence to: Pasquapina Ciarmela, email: p.ciarmela@univpm.it Maurizio Battino, email: m.a.battino@univpm.it Keywords: strawberry, uterine leiomyoma, fibrosis, apoptosis, ROS Received: September 20, 2016       Accepted: January 10, 2017       Published: February 15, 2017 ABSTRACT Uterine leiomyomas are highly prevalent benign tumors in reproductive aged women. Unfortunately, medical treatments are still limited and no preventive therapies have been developed. In the present study, we investigated the therapeutic effects of strawberry extract on uterine leiomyoma cells. Leiomyoma and myometrial cells were treated with strawberry (cultivar Alba ) extract (250 μg/ml) for 48 h to measure apoptosis, reactive oxygen species (ROS), oxidative phosphorylation (OCR, oxygen consumption rate) and glycolysis (ECAR, extracellular acidification rate) as well as fibrosis associated gene and/or protein expression. In leiomyoma cells, strawberry increased the percentage of apoptotic and dead cells. Strawberry significantly increased ROS concentration in leiomyoma cells, while decreased it in myometrial cells. After strawberry treatment, leiomyoma cells showed a significant decreased rate of ECAR, while OCR was unchanged in both myometrial and leiomyoma cells. Strawberry significantly decreased collagen1A1, fibronectin and versican mRNA expression in leiomyoma cells. The reduced protein expression of fibronectin was observed by strawberry extract in leiomyoma cells as well. Furthermore, strawberry was able to reduce activin A induced fibronectin, collagen1A1, and versican as well as activin A and PAI-1 mRNA expression in leiomyoma cells. This study suggests that strawberry can be developed as therapeutic and/or preventive agent for uterine leiomyomas.