The role of cell proliferation and extracellular matrix accumulation induced by food additive butylated hydroxytoluene in uterine leiomyoma

Yi Fen Chiang, Hsin Yuan Chen, Mohamed Ali, Tzong Ming Shieh, Yun Ju Huang, Kai Lee Wang, Hsin Yi Chang, Tsui Chin Huang, Yong Han Hong, Shih Min Hsia

Research output: Contribution to journalArticlepeer-review

Abstract

Leiomyoma is the most common benign uterine tumor in reproductive-age women. In-creasing 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 preser-vatives 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 phos-phoinositide 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.

Original languageEnglish
Article number3074
JournalNutrients
Volume13
Issue number9
DOIs
Publication statusPublished - Sep 2021

Keywords

  • Butylated hydroxytoluene
  • Environmental exposure
  • Extracellular matrix
  • Leiomyoma
  • Matrix metalloproteinase
  • Uterine fibroids

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

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