2. Academic Validation
  3. BF175 inhibits endometrial carcinoma through SREBP-regulated metabolic pathways in vitro

BF175 inhibits endometrial carcinoma through SREBP-regulated metabolic pathways in vitro

  • Mol Cell Endocrinol. 2021 Mar 1:523:111135. doi: 10.1016/j.mce.2020.111135.
Qiong Wang 1,  Ruofan Hu 1,  Weihua Li 2,  Yanhong Tai 3,  Weiting Gu 4,  Bhaskar C Das 5,  Fajun Yang 6,  Junyuan Ji 7,  Chenguang Wang 4,  Jie Zhou 8
Affiliations

Affiliations

  • 1 Department of Endocrinology and Metabolism, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
  • 2 Department of Obstetrics and Gynecology, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing, China.
  • 3 Department of Pathology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
  • 4 Departments of Cancer Biology, Stem Cell Biology and Regenerative Medicine, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
  • 5 Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • 6 Departments of Medicine and Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA.
  • 7 Department of Molecular and Cellular Medicine, Colleage of Medicine, Texas A&M University Health Science Center, College Station, TX, USA.
  • 8 Department of Endocrinology and Metabolism, Xijing Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: [email protected].
PMID: 33359761 DOI: 10.1016/j.mce.2020.111135
Abstract

Elevated lipogenesis is an important metabolic hallmark of rapidly proliferating tumor such as endometrial carcinoma (EC). The sterol regulatory element-binding protein 1 (SREBP1) is a master regulator of lipogenesis and involved in EC proliferation. BF175 is a novel chemical inhibitor of SREBP pathway, and has shown potent anti-lipogenic effects. However, the effect of BF175 on EC cells are yet to be determined. In the present study, we found that BF175 decreased cell viability, colony formation and migratory capacity, inducing Autophagy and mitochondrial related Apoptosis in EC cell line AN3CA. Z-VAD-FMK partially attenuated the effect of BF175 on AN3CA. In addition, BF175 significantly downregulated SREBPs and their downstream genes. The levels of free fatty acids and total Cholesterol were also inhibited. Microarray analysis suggested BF175 treatment obviously affected lipid metabolic pathways in EC. Taken together, we validated BF175 exhibited anti-tumor activity by targeting SREBP-dependent lipogenesis and inducing Apoptosis which mitochondrial pathway involved in, suggesting that it's potential as a novel therapeutic reagent for EC.

Keywords

BF175; Endometrial carcinoma; Lipid metabolism; SREBP.

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