Vitamin D as an effective treatment in human uterine leiomyomas independent of mediator complex subunit 12 mutation

Corachán, Ana; Trejo, María Gabriela; Carbajo-García, María Cristina; Monleón, Javier; Escrig, Julia; Faus, Amparo; Pellicer, A.; Cervelló, Irene; Ferrero, Hortensia

doi:10.1016/j.fertnstert.2020.07.049

Cited by 21 publications

(20 citation statements)

References 41 publications

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“…Expression of Wnt/β-catenin and TGF β pathway genes is, in fact, significantly increased in MED12-mutated leiomyomas. The authors of this study demonstrated that vitamin D exerted its antiproliferative action irrespective of MED12 mutation status [ 61 ].…”

Section: Mechanisms Underlying the Action Of Vitamin D In Uterine mentioning

confidence: 99%

Vitamin D: Mechanism of Action and Biological Effects in Uterine Fibroids

et al. 2021

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Uterine fibroids (UFs) are the most common benign gynecological tumors. It was estimated that fifty percent of women presenting with UFs has symptomatology that negatively influences their quality of life. Pharmacological and/or surgical treatments are frequently required, depending on the woman’s desire to preserve fertility, with a high impact on healthcare costs. Generally, the use of currently available pharmacological treatments may lead to side effects. Therefore, there is a growing interest in a natural and safe approach for UFs. In recent years, epidemiological studies reported a vitamin D deficiency in patients with UFs raised interest in the potential biological effects of vitamin D supplementation. In vitro studies proved vitamin D efficacy in inhibiting UFs growth by targeting pathways involved in the regulation of various biological processes, including proliferation, extracellular matrix (ECM) remodeling, DNA repair, signaling and apoptosis. However, clinical studies supported only in part the beneficial effects of vitamin D supplementation in reducing UFs growth and tumor volume. Randomized controlled trials and large population studies are mandatory as the potential clinical benefits are likely to be substantial.

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Section: Mechanisms Underlying the Action Of Vitamin D In Uterine mentioning

confidence: 99%

Vitamin D: Mechanism of Action and Biological Effects in Uterine Fibroids

et al. 2021

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“…Possibly it is due to, although leiomyomas with MED12 mutation had significant upregulation of Wnt pathway, leiomyomas without this mutation showed also an increase in this pathway, even though it was not significant. In addition, this study described that Wnt/b-Catenin pathway not only has a regulatory role on cell proliferation but also regulates TGFb signaling pathway (5). Since Wnt4 has been described as an intermediator between the Wnt/b-Catenin signaling and the AKT pathways (4), the dysregulated Wnt/b-Catenin pathway in leiomyomas could lead to extra activation of the TGFb signaling pathway that results in increased extracellular matrix (5) and increased cell proliferation by AKT activation (4).…”

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confidence: 87%

“…Previous studies have reported that uterine leiomyomas with MED12 mutation have up-regulated Wnt4 and b-Catenin proteins compared with adjacent myometrium, suggesting that MED12 mutation is implicated in uterine leiomyoma tumorigenesis through regulation of the Wnt/b-Catenin pathway (5). Therefore, a treatment that inhibits the Wnt/b-Catenin pathway could be effective to treat MED12mutated leiomyomas in a personalized way.…”

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confidence: 98%

“…Therefore, a treatment that inhibits the Wnt/b-Catenin pathway could be effective to treat MED12mutated leiomyomas in a personalized way. Several studies in cancer and uterine leiomyomas have suggested Vitamin D (VitD), specifically its active metabolite 1,25-dihydroxyvitamin D, as a noninvasive treatment to reduce tumor size due to its antitumorigenic and antiproliferative function through Wnt/b-Catenin pathway inhibition (5). Therefore, VitD could be proposed as a therapeutic option to treat MED12-mutated leiomyomas.…”

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confidence: 99%

“…Therefore, VitD could be proposed as a therapeutic option to treat MED12-mutated leiomyomas. However, a recent study demonstrated that VitD treatment inhibits cell proliferation and decreases expression of Wnt/b-Catenin pathway genes, especially Wnt4, and transforming growth factor (TGF) b pathway genes, such as TGFb3, in primary leiomyoma cells from MED12-mutated and nonmutated leiomyomas, suggesting an inhibitory action of VitD in these pathways independent of presence or absence of MED12 mutation (5). Possibly it is due to, although leiomyomas with MED12 mutation had significant upregulation of Wnt pathway, leiomyomas without this mutation showed also an increase in this pathway, even though it was not significant.…”

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confidence: 99%

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