Wnt/β-catenin signaling mediates the suppressive effects of diallyl trisulfide on colorectal cancer stem cells

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Abstract

Purpose

Cancer stem cells (CSCs) are responsible for colorectal cancer (CRC) initiation, growth, and metastasis. Garlic-derived organosulfur compound diallyl trisulfide (DATS) possesses cancer suppressive properties. Wnt/β-catenin signaling is a key target for CSCs inhibition. However, the interventional effect of DATS on colorectal CSCs has not been clarified. We aimed to illustrate the regulation of Wnt/β-catenin in DATS-induced colorectal CSCs inhibition.

Methods

Serum-free medium culture was used to enrich colorectal CSCs. SW480 and DLD-1 sphere-forming cells were treated with different concentrations of DATS for 5 days; LiCl and β-catenin plasmids were used to stimulate the activity of Wnt/β-catenin pathway. The size and number of colonspheres were detected by tumorsphere formation assay; the expression of colorectal CSCs-related genes was detected by Western blotting and qRT-PCR; the capacities of colorectal CSCs proliferation and apoptosis were detected by Cell Counting Kit-8, Hoechst 33258 cell staining and flow cytometry, respectively.

Results

The levels of colorectal CSCs markers were elevated in the tumorspheres cells. DATS efficiently suppressed the activity of colorectal CSCs, as evidenced by reducing the size and number of colonspheres, decreasing the expression of colorectal CSCs markers, promoting apoptosis and inhibiting the proliferation of colorectal CSCs. Moreover, DATS suppressed the activity of Wnt/β-catenin pathway, while upregulation of Wnt/β-catenin diminished the inhibitory effect of DATS on colorectal CSCs.

Conclusions

Wnt/β-catenin pathway mediates DATS-induced colorectal CSCs suppression. These findings support the use of DATS for targeting colorectal CSCs.

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Change history

  • 30 April 2018

    Unfortunately, the online published article has error in Figure 4. The correct Figure 4 is given here.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (No. 81573139, No. 81373005, No. 81602839), the National Basic Research Program of China (973 Program) (No. 2013CB910303), and by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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Correspondence to Cai-Yun Zhong or Hong-Yu Han.

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Zhang, Q., Li, XT., Chen, Y. et al. Wnt/β-catenin signaling mediates the suppressive effects of diallyl trisulfide on colorectal cancer stem cells. Cancer Chemother Pharmacol 81, 969–977 (2018). https://doi.org/10.1007/s00280-018-3565-0

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Keywords

  • Diallyl trisulfide
  • Colorectal cancer stem cells
  • Wnt/β-catenin signaling
  • Inhibition