Alantolactone inhibits cervical cancer progression by downregulating BMI1

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...

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Autores principales:	Xiaodong Sun, Hongxia Xu, Tianyu Dai, Lixia Xie, Qiang Zhao, Xincai Hao, Yan Sun, Xuanbin Wang, Nan Jiang, Ming Sang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/62aa2beeff9b416299876423bba6445c
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spelling	oai:doaj.org-article:62aa2beeff9b416299876423bba6445c2021-12-02T17:20:11ZAlantolactone inhibits cervical cancer progression by downregulating BMI110.1038/s41598-021-87781-z2045-2322https://doaj.org/article/62aa2beeff9b416299876423bba6445c2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87781-zhttps://doaj.org/toc/2045-2322Abstract 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.Xiaodong SunHongxia XuTianyu DaiLixia XieQiang ZhaoXincai HaoYan SunXuanbin WangNan JiangMing SangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaodong Sun Hongxia Xu Tianyu Dai Lixia Xie Qiang Zhao Xincai Hao Yan Sun Xuanbin Wang Nan Jiang Ming Sang Alantolactone inhibits cervical cancer progression by downregulating BMI1
description	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.
format	article
author	Xiaodong Sun Hongxia Xu Tianyu Dai Lixia Xie Qiang Zhao Xincai Hao Yan Sun Xuanbin Wang Nan Jiang Ming Sang
author_facet	Xiaodong Sun Hongxia Xu Tianyu Dai Lixia Xie Qiang Zhao Xincai Hao Yan Sun Xuanbin Wang Nan Jiang Ming Sang
author_sort	Xiaodong Sun
title	Alantolactone inhibits cervical cancer progression by downregulating BMI1
title_short	Alantolactone inhibits cervical cancer progression by downregulating BMI1
title_full	Alantolactone inhibits cervical cancer progression by downregulating BMI1
title_fullStr	Alantolactone inhibits cervical cancer progression by downregulating BMI1
title_full_unstemmed	Alantolactone inhibits cervical cancer progression by downregulating BMI1
title_sort	alantolactone inhibits cervical cancer progression by downregulating bmi1
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/62aa2beeff9b416299876423bba6445c
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_version_	1718381028684333056

Alantolactone inhibits cervical cancer progression by downregulating BMI1

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