1. Academic Validation
  2. Limonin attenuates the stemness of breast cancer cells via suppressing MIR216A methylation

Limonin attenuates the stemness of breast cancer cells via suppressing MIR216A methylation

  • Biomed Pharmacother. 2019 Apr;112:108699. doi: 10.1016/j.biopha.2019.108699.
Zhou Su 1 Caihong Wang 2 Deyu Chang 3 Xiuna Zhu 4 Chunmei Sai 5 Jian Pei 6
Affiliations

Affiliations

  • 1 Department of Pharmacy, Rizhao People's Hospital of Shandong Province, 126 Tai'an Road, Rizhao 276800, China.
  • 2 Department of Pharmacy, Rizhao City Maternal and Child Health Care Hospital, Shandong Province, Rizhao 276800, China.
  • 3 Department of Pharmacy, Rizhao People's Hospital of Shandong Province, Rizhao 276800, China.
  • 4 Department of Surgery, Rizhao People's Hospital of Shandong Province, Rizhao 276800, China.
  • 5 School of pharmacy, Jining Medical University, Rizhao City, Shandong, China.
  • 6 Department of Pharmacy, Rizhao People's Hospital of Shandong Province, 126 Tai'an Road, Rizhao 276800, China. Electronic address: jianpei_RPH@163.com.
Abstract

Limonin has been shown to exert anti-inflammatory effects, however, its roles in tumor progression remain unclear. This work aims to investigate the roles and related mechanism of limonin in the stemness of breast Cancer cells. Here, we found that limonin attenuated the stemness of breast Cancer cells in a concentration-dependent manner, evident by the decreasing the capacity of cell spheroid formation, expression of stemness markers and ALDH1 activity, whereas had no toxicity on non-tumorigenic cells. Additionally, limonin enhanced adriamycin sensitivity of breast Cancer cells and attenuated adriamycin resistance in adriamycin-resistant breast Cancer cells. Mechanistically, limonin decreased MIR216A methylation level and thus increased miR-216a-3p expression. Furthermore, miR-216a-3p could directly bind to WNT3A and thus inactivated Wnt/β-catenin pathway. Therefore, our results indicate that limonin could attenuate the stemness and chemoresistance via inhibiting MIR216A methylation and subsequently suppressing Wnt/β-catenin pathway.

Keywords

Breast cancer; Limonin; Stemness; Wnt/β-catenin; miR-216a-3p.

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