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

Milijana Janjusevic,Tamara Y Forbes-Hernandez,Stefano Raffaele Giannubilo,Pasquapina Ciarmela,Mario Castellucci,Bruno Mezzetti,Francesca Giampieri,Luca Mazzoni,Maurizio Battino,Andrea Ciavattini,Stefania Greco,Franco Capocasa,Md Soriful Islam,Massimiliano Gasparrini

doi:10.18632/oncotarget.15333

Milijana Janjusevic, Tamara Y Forbes-Hernandez + Show 12 more

Open Access

https://doi.org/10.18632/oncotarget.15333

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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.

Highlights

Uterine leiomyomas are benign smooth muscle tumors originating from the myometrium [1]
Primary myometrial and leiomyoma cells were treated with strawberry extract at different concentrations (50, 100, 250, 500 μg/ml) for 24 h, 48 h and 72 h, and cell viability was determined by MTT assay
In order to evaluate the effect of strawberries in cell viability, myometrial and leiomyoma cells were treated with strawberry extract at 250 μg/ml for 48 h, and the apoptotic/dead/live cell numbers were analysed using the TaliTM apoptosis assay kit

Summary

Introduction

Uterine leiomyomas (fibroids or myomas) are benign smooth muscle tumors originating from the myometrium [1]. 25% of women shows significant clinical symptoms, such as abnormal uterine bleeding, abdominal pain and discomfort, pregnancy complications and even infertility [1, 3]. This complicated disease exerts an enormous burden on health care system worldwide. Leiomyoma treatment has mainly been surgical some medical therapies are available for women who wish to preserve their uterus These include www.impactjournals.com/oncotarget gonadotropin-releasing hormone (GnRH) agonists (leuprolide acetate), GnRH antagonists (cetrorelix acetate), selective progesterone receptor modulators (ulipristate acetate and asoprisnil), antiprogestin (mifepristone), etc. There is an urgent need to develop safe and effective nonsurgical treatments for women with uterine fibroids

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