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Baicalin Antagonizes Prostate Cancer Stemness via Inhibiting Notch1/NF-κB Signaling Pathway

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Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To investigate the molecular mechanisms underlying the effect of baicalin on prostate cancer (PCa) progression both in vivo and in vitro.

Methods

The in situ PCa stem cells (PCSCs)-injected xenograft tumor models were established in BALB/c nude mice. Tumor volume and weight were respectively checked after baicalin (100 mg/kg) treatment. Hematoxylin-eosin (HE) staining was used to observe the growth arrest and cell necrosis. mRNA expression levels of acetaldehyde dehydrogenase 1 (ALDH1), CD44, CD133 and Notch1 were determined by reverse transcription-polymerase chain reaction. Protein expression levels of ALDH1, CD44, CD133, Notch1, nuclear factor κB (NF-κB) P65 and NF-κB p-P65 were detected by Western blot. Expression and subcellular location of ALDH1, CD44, CD133, Notch1 and NF-κB p65 were detected by immunofluorescence analysis. In vitro, cell cycle distribution and cell apoptosis of PC3 PCSCs was assessed by flow cytometry after baicalin (125 µmol/L) treatment. The migration and invasion abilities of PCSCs were assessed using Transwell assays. Transmission electron microscopy scanning was utilized to observe the structure and autophagosome formation of baicalin-treated PCSCs. In addition, PCSCs were infected with lentiviruses expressing human Notch1.

Results

Compared with the control group, the tumor volume and weight were notably reduced in mice treated with 100 mg/kg baicalin (P<0.05 or P<0.01). Histopathological analysis showed that baicalin treatment significantly inhibited cell proliferation and promoted cell apoptosis. Furthermore, baicalin treatment reduced mRNA and protein expression levels of CD44, CD133, ALDH1, and Notch1 as well as the protein expression of NF-κB p-P65 in the xenograft tumor (P<0.01). In vitro, the cell proliferation of PCSCs was significantly attenuated after treatment with 125 µmol/L baicalin for 72 h (P<0.01). The cell migration and invasion rates were decreased following treatment with baicalin for 48 and 72 h (P<0.01). Baicalin notably induced cell apoptosis and seriously damaged the structure of PCSCs. The mRNA and protein expressions of CD133, CD44, ALDH1 and Notch1 in PCSCs were significantly downregulated following baicalin treatment (P<0.01). Importantly, the inhibitory effects of baicalin on PCa progression and stemness were reversed by Notch1 overexpression (P<0.05 or P<0.01).

Conclusion

Mechanistically, baicalin exhibited a potential therapeutic effect on PCa via inhibiting the Notch1/NF-κB signaling pathway and its mediated cancer stemness.

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Author information

Authors and Affiliations

  1. Department of Urology, Hubei University of Traditional Chinese Medicine, Wuhan, 430065, China

    Ming-hui Wu & Kun Wu

  2. Department of Urology, Chongqing Jiang** District Hospital of Chinese Medicine, Chongqing, 402260, China

    Yuan-bing Zhu, Da-chuan Li, Huan Yang & Hong Zeng

Authors
  1. Ming-hui Wu
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  2. Kun Wu
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  3. Yuan-bing Zhu
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  4. Da-chuan Li
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  5. Huan Yang
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  6. Hong Zeng
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Contributions

Wu MH performed the experiments and wrote the paper. Wu K performed the experiments and analyzed the data. Zhu YB, Li DC and Yang H performed the experiments. Zeng H designed the study, reviewed the paper and provided the funding. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Hong Zeng.

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The authors declare that they have no competing interests.

Additional information

Supported by the Science and Health Joint Chinese Medical Research Project of Chongqing Municipal Health Committee (No. 2019ZY023447)

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Wu, Mh., Wu, K., Zhu, Yb. et al. Baicalin Antagonizes Prostate Cancer Stemness via Inhibiting Notch1/NF-κB Signaling Pathway. Chin. J. Integr. Med. 29, 914–923 (2023). https://doi.org/10.1007/s11655-023-3595-2

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  • DOI: https://doi.org/10.1007/s11655-023-3595-2

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