Romina: A powerful strawberry with in vitro efficacy against uterine leiomyoma cells

Abstract

Uterine leiom yomas are benign tumors highly prevalent in reproductive women. In thecurrent study, initially, we aimed to screen five different strawberry cultivars (Alba, Clery, Portola, Tecla, and Romina) to identify efficient cultivars in terms of phytochemical characterization and biological properties by measuring phenolic and anthocyanin content as well as antioxidant capacity, and by measuring apoptotic rate and reactive oxygen species (ROS) production in uterine leiomyoma cells. Next, we focused on the most efficient ones, cultivar Alba (A) and Romina (R) as well as Romina anthocyanin (RA) fraction for their ability to regulate oxidative phosphorylation (oxygen consumption rate [OCR]) glycolysis (extracellular acidification rate [ECAR]), and also fibrosis. Leiomyoma and myometrial cells were treated with a methanolic extract of A and R (250 μg/ml) or with RA (50 μg/ml) for 48 hr to measure OCR and ECAR, as well as gene expression associated with fibrosis. In the leiomyoma cells, RA was more effective in inducing apoptosis and increasing intracellular ROS levels, followed by R and A. In myometrial cells, all strawberry treatments increased the cellular viability and decreased ROS concentrations. Leiomyoma cells showed also a significant decrease in ECAR, especially after RA treatment, while OCR was slightly increased in both myometrial and leiomyoma cells. R and RA treatment significantly decreased collagen 1A1, fibronectin, versican, and activin A messenger RNA expression in leiomyoma cells. In conclusion, this study suggests that Romina, or its anthocyanin fraction, can be developed as a therapeutic and/or preventive agent for uterine leiomyomas, confirming the healthy effects exerted by these fruits and their bioactive compounds. K E Y W O R D S apoptosis, cultivars, fibrosis, glycolysis, Romina, strawberry, uterine leiomyoma J Cell Physiol. 2019;234:7622-7633. wileyonlinelibrary.com/journal/jcp 7622 |

The Evolving Role of Natural Compounds in the Medical Treatment of Uterine Fibroids

“…A recent study tested five different strawberry cultivars to identify which one presents the best phytochemical profile as an anti-UF agent. Authors found that Alba (same as in study above) and Romina cultivars presented the best results, with decreased collagen 1A1, fibronectin, versican, and activin A mRNA expression in UF cells [169]. Strawberry and its potent anthocyanins might offer therapeutic or preventive spectrum in UF treatment.…”

“…Plants that are rich in those pigments include blueberries, raspberries or strawberries [167]. According to two studies, strawberries anthocyanin are of special interest in UFs [168][169][170]. Strawberries have anti-inflammatory, anti-oxidative, anti-proliferative, and genomic protective effects [169,171].…”

“…According to two studies, strawberries anthocyanin are of special interest in UFs [168][169][170]. Strawberries have anti-inflammatory, anti-oxidative, anti-proliferative, and genomic protective effects [169,171]. Islam et al studied the effect of a variety of strawberry Alba cultivar extract on apoptosis, fibrosis, oxidation, and other processes in myometrium and UF cells.…”

Evidence-Based Management of Uterine Fibroids With Botanical Drugs-A Review

“…Following that, the same group of researchers investigated the anti-UF activity of five different cultivars of strawberry. It was identified that Romina followed by the Alba cultivar produced the most promising anti-UF activity, which suggests its potential in using strawberry extract as an alternative treatment for UF ( Giampieri et al, 2019 ).…”

Strawberry bioactive compounds and human health: The exciting story of an unbelievable bet

“…We also highlighted that the anticancer activities of strawberry were ascribed to its capability to regulate some genes involved in different cancer‐related molecular pathways: for example, in uterine benign leiomyomas, strawberry extract (250 μg/ml for 48 hr) and its anthocyanin fraction (50 μg/ml for 48 hr) promoted apoptosis, increased the levels of ROS, affected glycolysis, and reduced the expression of genes involved in fibrosis, a feature of this type of tumor, such as collagen 1A1, fibronectin, versican, and activin A (Giampieri et al., 2019), whereas in murine breast N202/1A (with high levels of HER2/neu oncogene) and N202/1E (with low levels of HER2/neu oncogene) cancer cells, strawberry extract (175–200 μg/ml for 48 hr) and its anthocyanin fraction (175–200 μg/ml for 48 hr) were able to play antiproliferative effects, through the induction of oxidative stress and apoptosis, by regulating the expression of several proteins involved in the antioxidant system, in apoptosis and in mitochondrial biogenesis and functionality, including AMPK, PGC‐1α, SIRT3, nuclear factor erythroid 2‐related factor 2 (Nrf2), caspase 3, and cytochrome b–c1 complex subunit 1 (Mazzoni et al., 2019). Similarly, in murine breast A17 cancer cell line, strawberry (0.5, 1, 2.5, and 5 mg/ml for 48 hr) stopped cell cycle in phase G1 and decreased cellular mobility by regulating the expression of several genes involved in invasion, cellular migration, and adhesion processes, such as the colony stimulating factor 1 (Csf1), the nuclear receptor subfamily 4, group A, member 3 (Nr4a3), the melanoma cell adhesion molecule (Mcam), SET nuclear proto‐oncogene (SET), matrix metalloproteinases 10 and 3 (Mmp10 and Mmp3), and integrin beta 3; interestingly, the anticancer activities of strawberry were further confirmed in an in vivo study, where the growth of A17 cells orthotopically transplanted into FVB syngeneic mice was inhibited by strawberry consumption (15% of total diet calories) (Amatori et al., 2017).…”