Korean Journal of Plant Resources (한국자원식물학회지)

The Plant Resources Society of Korea (한국자원식물학회)
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Suppression of Migration and Invasion by Alnus hirsuta in Human Hepatocellular Carcinoma Cells

  • Bo-Ram Kim (Honam National Institute of Biological Resources) ;
  • Su Hui Seong (Honam National Institute of Biological Resources) ;
  • Tae-Su Kim (Honam National Institute of Biological Resources) ;
  • Jin-Ho Kim (Honam National Institute of Biological Resources) ;
  • Chan Seo (Honam National Institute of Biological Resources) ;
  • Ha-Nul Lee (Honam National Institute of Biological Resources) ;
  • Sua Im (Honam National Institute of Biological Resources) ;
  • Jung Eun Kim (Honam National Institute of Biological Resources) ;
  • Ji Min Jung (Honam National Institute of Biological Resources) ;
  • Jung Up Park (Honam National Institute of Biological Resources) ;
  • Kyung-Min Choi (Honam National Institute of Biological Resources) ;
  • Jin-Woo Jeong (Honam National Institute of Biological Resources)
  • Received : 2023.05.04
  • Accepted : 2023.05.19
  • Published : 2023.06.01
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Abstract

Hepatocellular carcinoma (HCC) has a poor prognosis and high metastasis and recurrence rates. Although extracts of Alnus hirsuta (Turcz. ex Spach) Rupr. (AH) have been demonstrated to possess potential anti-inflammatory and anti-cancer activities, the underlying mechanism of AH in HCC treatment remains to be elucidated. We investigated the effects and potential mechanisms of AH on migration and invasion of Hep3B cells. Within the non-cytotoxic concentration range, AH significantly inhibited motility and invasiveness of Hep3B cells in a concentration-dependent manner. Inhibitory effects of AH on cell invasiveness are associated with tightening of tight junctions (TJs), as demonstrated by an increase in transepithelial electrical resistance. Immunoblotting indicated that AH decreased levels of claudins, which form major components of TJs and play key roles in the control and selectivity of paracellular transport. Furthermore, AH inhibited the expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9 and simultaneously increased the levels of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. These effects were related to inactivation of the phosphoinositide 3-kinase (PI3K)/AKT pathway in Hep3B cells. Therefore, AH inhibits migration and invasion of Hep3B cells by inhibiting the activity of MMPs and tightening TJs through suppression of claudin expression, possibly by suppressing the PI3K/AKT signaling pathway.

Keywords

Acknowledgement

This work was supported by a grant from the Honam National Institute of Biological Resources (HNIBR), funded by the Ministry of Environment (MOE) of the Korea (HNIBR202302115) and Korea Environment Industry & Technology Institute (KEITI) through project to make multi-ministerial national biological research resources more advanced, funded by Korea Ministry of Environment (MOE) (RS-2023-00230402).

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