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Journal of Cancer Prevention

Original Article

J Cancer Prev 2023; 28(4): 185-193

Published online December 30, 2023

© Korean Society of Cancer Prevention

Induction of Hepatocellular Carcinoma Cell Cycle Arrest and Apoptosis by Dendropanax morbifera Leveille Leaf Extract via the PI3K/AKT/mTOR Pathway

Gi Dae Kim

Department of Food and Nutrition, Kyungnam University, Changwon, Korea

Correspondence to :
Gi Dae Kim, E-mail:,

Received: November 10, 2023; Revised: December 4, 2023; Accepted: December 6, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Liver cancer is prevalent worldwide and associated with a high mortality rate. Therefore, developing novel drugs derived from natural products to reduce the side effects of chemotherapy is urgently needed. In this study, the inhibitory effect of Dendropanax morbifera Leveille extract (DME) on growth of hepatocellular carcinoma (HCC) cells and its underlying mechanisms were investigated. DME suppressed the growth, migration, and invasion of SK-Hep1 human HCC cells. It also reduced the expression of the G0/G1 phase regulator proteins cyclin-dependent kinase (CDK) 4, cyclin D, CDK2, and cyclin E, thereby inducing G0/G1 arrest. Moreover, DME treatment reduced the expression of antiapoptotic proteins, including caspase-9, caspase-3, PARP, and Bcl-2 and increased the expression of the proapoptotic protein, Bax. DME also increased reactive oxygen species production and reduced the cellular uptake of rhodamine 123. DME treatment increased the levels of p-p38 and p-FOXO3a in a dose-dependent manner and decreased those of p-PI3K, p-AKT, p-mTOR, and p-p70 in SK-Hep1 cells. In addition, combined treatment with DME and LY294002, an AKT inhibitor, significantly reduced p-AKT levels. In summary, these results show that the PI3K/AKT/mTOR signaling pathway is involved in DME-mediated inhibition of proliferation, migration, and invasiveness, and induction of apoptosis of HCC cells.

Keywords: Dendropanax morbifera Leveille, Hepatocellular carcinoma, Cell cycle arrest, Apoptosis

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