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Alantolactone inhibits cervical cancer progression by downregulating BMI1

Authors
  • Sun, Xiaodong1
  • Xu, Hongxia1
  • Dai, Tianyu2
  • Xie, Lixia1
  • Zhao, Qiang1
  • Hao, Xincai1
  • Sun, Yan1
  • Wang, Xuanbin1
  • Jiang, Nan3
  • Sang, Ming1
  • 1 Hubei University of Medicine, Shiyan, 442000, People’s Republic of China , Shiyan (China)
  • 2 Tongji University, Shanghai, 200092, People’s Republic of China , Shanghai (China)
  • 3 Hubei Province Academy of Traditional Chinese Medicine, Wuhan, 430061, People’s Republic of China , Wuhan (China)
Type
Published Article
Journal
Scientific Reports
Publisher
Springer Nature
Publication Date
Apr 29, 2021
Volume
11
Issue
1
Identifiers
DOI: 10.1038/s41598-021-87781-z
Source
Springer Nature
License
Green

Abstract

Cervical cancer is the second most common cancer in women. Despite advances in cervical cancer therapy, tumor recurrence and metastasis remain the leading causes of mortality. High expression of BMI1 is significantly associated with poor tumor differentiation, high clinical grade, and poor prognosis of cervical cancer, and is an independent prognostic factor in cervical carcinoma. Alantolactone (AL), a sesquiterpene lactone, exhibits potent anti-inflammatory and anticancer activities. In this paper, we investigated the mechanism of AL in reducing the proliferation, migration, and invasion of HeLa and SiHa cervical cancer cells as well as its promotion of mitochondrial damage and autophagy. BMI1 silencing decreased epithelial-mesenchymal transformation-associated proteins and increased autophagy-associated proteins in HeLa cells. These effects were reversed by overexpression of BMI1 in HeLa cells. Thus, BMI1 expression is positively correlated with invasion and negatively correlated with autophagy in HeLa cells. Importantly, AL decreased the weight, volume, and BMI1 expression in HeLa xenograft tumors. Furthermore, the structure of BMI1 and target interaction of AL were virtually screened using the molecular docking program Autodock Vina; AL decreased the expression of N-cadherin, vimentin, and P62 and increased the expression of LC3B and Beclin-1 in xenograft tumors. Finally, expression of BMI1 increased the phosphorylation of STAT3, which is important for cell proliferation, survival, migration, and invasion. Therefore, we suggest that AL plays a pivotal role in inhibiting BMI1 in the tumorigenesis of cervical cancer and is a potential therapeutic agent for cervical cancer.

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