{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T02:44:00Z","timestamp":1790217840101,"version":"4.1.0"},"reference-count":58,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T00:00:00Z","timestamp":1630368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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\u2019s 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.<\/jats:p>","DOI":"10.3390\/nu13093074","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T21:59:45Z","timestamp":1630447185000},"page":"3074","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The Role of Cell Proliferation and Extracellular Matrix Accumulation Induced by Food Additive Butylated Hydroxytoluene in Uterine Leiomyoma"],"prefix":"10.3390","volume":"13","author":[{"given":"Yi-Fen","family":"Chiang","sequence":"first","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Yuan","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Department of Nutrition, I-Shou University, Kaohsiung 84001, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9675-6691","authenticated-orcid":false,"given":"Mohamed","family":"Ali","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzong-Ming","family":"Shieh","sequence":"additional","affiliation":[{"name":"School of Dentistry, College of Dentistry, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Ju","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Department of Biotechnology and Food Technology, Southern Taiwan University of Science and Technology, Tainan 71005, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3058-3804","authenticated-orcid":false,"given":"Kai-Lee","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nursing, Ching Kuo Institute of Management and Health, Keelung 20301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2742-0676","authenticated-orcid":false,"given":"Hsin-Yi","family":"Chang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7873-132X","authenticated-orcid":false,"given":"Tsui-Chin","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Han","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Nutrition, I-Shou University, Kaohsiung 84001, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2888-2618","authenticated-orcid":false,"given":"Shih-Min","family":"Hsia","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"School of Food and Safety, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Nutrition Research Center, Taipei Medical University Hospital, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1177\/1933719111432867","article-title":"Medical treatment of uterine leiomyoma","volume":"19","author":"Sabry","year":"2012","journal-title":"Reprod. 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