Eupatorium lindleyanum DC. sesquiterpene fraction F1012-2 regulates p53/NF-κB signaling pathways in human breast cancer

Authors

  • Xinyu Wang College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 311402, China
  • Jiajin Xu College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 311402, China
  • Yixuan Tao College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 311402, China
  • Xiangrong Fan College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 311402, China
  • Xintong Shen College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 311402, China
  • Shasha Tian College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 311402, China

DOI:

https://doi.org/10.2298/ABS220630028W

Keywords:

Eupatorium lindleyanum DC., F1012-2, p53, Nuclear Factor-κB (NF-κB), triple-negative breast cancer

Abstract

Paper description:

  • F1012-2 is a novel sesquiterpene lactone isolated from the Chinese herbal medicine Eupatorium lindleyanum, whose regulation is ill-defined in breast cancer progression.
  • We investigated the anticancer activities of F1012-2 on human breast cancer and its effect on the crosstalk between p53 and NF-κB signaling pathways.
  • F1012-2 exhibited an inhibitory effect on triple-negative breast cancer (TNBC), and this is mainly related to the regulation of p53/NF-κB signaling pathways.
  • F1012-2 co-regulated p53 and NF-κB signaling pathways, thus providing multiple targets for therapeutic intervention in TNBC.

Abstract: F1012-2, a novel sesquiterpene lactone isolated from the Chinese herbal medicine Eupatorium lindleyanum DC, exhibits an antitumor effect. In this study, we investigated the anticancer activities of F1012-2 on ten human breast cancer lines and demonstrated significantly lower IC50 values for triple-negative breast cancer (TNBC) than for non-TNBC cell lines. The transcription factors p53 and nuclear factor-κB (NF-κB) are important regulators of tumorigenesis. F1012-2 not only depleted mutant p53, but also activated wild-type p53. F1012-2 reduced the expression of phosphorylated p65 and p105 NF-κB family members and coregulated p53, NF-κB members and their dependent targets. To further clarify the key role of p53, lentivirus small hairpin RNA (shRNA) infection was used to knockdown p53 in MDA-MB-231 cells. F1012-2 significantly reduced the inhibitory effect on cell proliferation and apoptosis, while the levels of p53, NF-κB family members and their dependent genes were not significantly different. F1012-2 exhibited a significant antitumor effect and reduced the expression of p53 in MDA-MB-231 xenografts. Taken together, our results show that F1012-2 exhibited an inhibitory effect on TNBC and affected the regulation of p53/NF-κB signaling pathways.

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Published

2022-10-05

How to Cite

1.
Wang X, Xu J, Tao Y, Fan X, Shen X, Tian S. Eupatorium lindleyanum DC. sesquiterpene fraction F1012-2 regulates p53/NF-κB signaling pathways in human breast cancer. Arch Biol Sci [Internet]. 2022Oct.5 [cited 2024Apr.24];74(3):291-9. Available from: https://serbiosoc.org.rs/arch/index.php/abs/article/view/7883

Issue

Vol. 74 No. 3 (2022)

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Articles

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Copyright (c) 2022 Xinyu Wang, Jiajin Xu, Yixuan Tao, Xiangrong Fan, Xintong Shen, Shasha Tian

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