Abstract
Leiomyoma is the most common benign uterine tumor in reproductive-age women. Increasing numbers of studies are focusing on the effects of environmental exposure on the incidence and progression of tumors. One major step taken in the food industry is the addition of food preservatives to maintain freshness. Butylated hydroxytoluene (BHT) is a synthetic phenolic antioxidant, which is widely used as an additive to develop fat-soluble characteristics, as well as in cosmetics and rubber. Previous studies also highlighted that BHT may be related to increased fibrosis capacity and carcinogenic effects. In this study, we explored the effects of the commonly used food additive BHT on leiomyoma progression, and the related mechanism. The exposure of the ELT-3 leiomyoma cell line to BHT for 48 h increased the proliferative effect. Since leiomyoma progression is related to increases in extracellular matrix (ECM) accumulation and matrix metalloproteinase (MMP), BHT could effectively increase ECM-related protein expression, as well as MMP-2 and MMP-9 protein expression. This increase in ECM, in response to BHT, may be linked to the activation of the phosphoinositide 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) signaling pathway. Through PI3K inhibition, BHT’s effect on leiomyoma progression could be partially modulated. These results suggest the harmful effect of BHT exposure on leiomyoma progression may relate to PI3K modulation. However, an in vivo study is necessary to confirm these findings.
Highlights
Leiomyoma are the most common benign uterine tumors in reproductive-age women, with an incidence rate of more than 70% [1,2]
We used MTT as the cell proliferation assay to evaluate the changes in cell viability following Butylated hydroxytoluene (BHT) exposure in ELT-3 cells
All the concentrations used for the 48 h treatments could significantly increase leiomyoma cell viability (Figure 1A,B), indicating the potential role of BHT in leiomyoma cell viability
Summary
Leiomyoma (aka uterine fibroids) are the most common benign uterine tumors in reproductive-age women, with an incidence rate of more than 70% [1,2]. Leiomyoma is categorized according to its location. The International Federation of Gynecology and Obstetrics (FIGO) classified the definition, submucosal myomas 0, 1, 2) and intramural myomas (FIGO type 3, 4, 5). Submucosal myomas were located below the endometrium, and intramural myomas were located within the uterine wall [3,4]. The main symptoms of leiomyoma are abnormal vaginal bleeding, lower abdominal pain, and bulk symptoms [5]. Studies have reported links between leiomyoma and recurrent miscarriage and infertility [5,6]
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