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Lens culinaris agglutinin inhibits human hepatoma cell migration via mannose and fucose-mediated ERK1/2 and JNK1/2/3 signalling pathway

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Abstract

Background

Hepatocellular carcinoma (HCC) is the main types of primary liver cancer, which shows some abnormal glycosylation, such as the increase of fucose. Lens culinaris agglutinin (LCA), a natural plant lectin that can bind to mannose and fucose, has been reported to be antiproliferative to may tumors. However, the effect of LCA on the vitality and migration ability of human hepatoma cells is not demonstrated. Therefore, the aim of this study is to investigate the effects of LCA on vitality and migration in human hepatoma cells and its potential mechanisms.

Methods and results

LCA had no significant effect on viability of human hepatoma cells (HCCLM3, MHCC97L and HepG2) and hepatocytes (L02) by CCK-8 kit, but it could inhibit human hepatoma cells migration significantly without affecting hepatocytes by Transwell method. Sugar inhibition assay was used to verify the possible binding site between LCA and human hepatoma cells. The result showed that Mannose- and fucose- related sites were associated with LCA inhibiting human hepatoma cells migration. Moreover, LCA could affect HCCLM3 migration by activating ERK1/2 and JNK1/2/3 signalling pathways. LCA did not affect MMP-2 and MMP-9 of HCCLM3 through gelatinase zymography. However, the results of immunofluorescence standing showed that LCA could reduce the F-actin formation in HCCLM3 via ERK1/2 and JNK1/2/3 signalling pathways.

Conclusions

LCA might inhibit human hepatoma cell migration by reducing the F-actin formation via the mannose and fucose-mediated ERK1/2 and JNK1/2/3 signalling pathway. This result will deepen people’s understanding on plant lectin as a drug in tumor glycobiology.

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Acknowledgements

This work was supported by the Science and Technology Research Program of Chongqing Municipal Education Commission [KJQN201800601, KJQN201900644] and the Natural Science Foundation of Chongqing [cstc2020jcyj-msxmX0760].

Funding

This work was supported by the Science and Technology Research Program of Chongqing Municipal Education Commission [KJQN201800601, KJQN201900644] and the Natural Science Foundation of Chongqing [cstc2020jcyj-msxmX0760].

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Authors and Affiliations

  1. Chongqing Engineering Research Center of Medical Electronics and Information Technology, College of Bioinformatics, Chongqing University of Posts and Telecommunications, 400065, Chongqing, China

    Haoran Jiang, Xianxin Wen, Xue Zhang, Xianhua Zhong, Zhangyong Li & Bingyu Zhang

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  1. Haoran Jiang
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  2. Xianxin Wen
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Conceptualization: Bingyu Zhang and Zhangyong Li; Methodology: Bingyu Zhang and Haoran Jiang; Formal analysis and investigation: Haoran Jiang, Xianxin Wen and Xue Zhang; Writing-original draft preparation: Haoran Jiang; Review and editing: Bingyu Zhang; Resources: Bingyu Zhang and Xianhua Zhong. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Bingyu Zhang.

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Jiang, H., Wen, X., Zhang, X. et al. Lens culinaris agglutinin inhibits human hepatoma cell migration via mannose and fucose-mediated ERK1/2 and JNK1/2/3 signalling pathway. Mol Biol Rep 49, 7665–7676 (2022). https://doi.org/10.1007/s11033-022-07582-z

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