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Planta Med 2020; 86(10): 717-727
DOI: 10.1055/a-1167-4284
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Artemisiae Iwayomogii Herba Inhibits Growth, Motility, and the PI3K/AKT/mTOR Signaling Pathway in Hepatocellular Carcinoma Cells

Juyoung Kim‡
1   Department of Biomedical Sciences, College of Medicine, Inha University, Incheon, Korea
,
Kyung Hee Jung‡
1   Department of Biomedical Sciences, College of Medicine, Inha University, Incheon, Korea
,
Jin Gyu Choi‡
2   Department of Oriental Pharmaceutical Science, College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, Seoul, Korea
,
Myung Sook Oh
2   Department of Oriental Pharmaceutical Science, College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, Seoul, Korea
3   Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, Korea
,
Soon-Sun Hong
1   Department of Biomedical Sciences, College of Medicine, Inha University, Incheon, Korea
› Author AffiliationsSupported by: National Research Foundation of Korea 2018R1A2A1A05077263
Supported by: National Research Foundation of Korea 2019M3E5D1A02069621
Supported by: National Research Foundation of Korea 2014009392
Further Information

Publication History

received 07 October 2019
revised 19 April 2020

accepted 24 April 2020

Publication Date:
19 May 2020 (online)

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Abstract

Artemisia gmelinii (Artemisia iwayomogi) has been used in traditional medicine to cure various infectious diseases such as cholecystitis, hepatitis, and jaundice. In this study, the Artemisiae Iwayomogii Herba ethanol extract was investigated for the ability to inhibit growth of hepatocellular carcinoma and its underlying mechanism involved. The antiproliferative effect of Artemisiae Iwayomogii Herba ethanol extract was evaluated using cell viability and proliferation assays. The effect of Artemisiae Iwayomogii Herba ethanol extract on apoptosis was measured using western blotting, terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling staining, JC-1 staining, cytochrome c release, immunohistochemistry, and immunofluorescence in ex vivo mouse xenografts. Artemisiae Iwayomogii Herba ethanol extract inhibited hepatocellular carcinoma cell growth and proliferation in a dose-dependent manner. The apoptotic effect of Artemisiae Iwayomogii Herba ethanol extract was observed via increased levels of cleaved caspase-3 and cleaved PARP, as well as elevated numbers of terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling-positive apoptotic cells. Artemisiae Iwayomogii Herba ethanol extract also decreased XIAP and Mcl-1 expression via loss of mitochondrial membrane potential. Additionally, Artemisiae Iwayomogii Herba ethanol extract inhibited hepatocellular carcinoma cell invasion and migration. In the ex vivo model, Artemisiae Iwayomogii Herba ethanol extract significantly inhibited tumor cell proliferation and increased the number of apoptotic cells with more activated cleaved caspase-3. A mechanistic study revealed that Artemisiae Iwayomogii Herba ethanol extract effectively suppressed the PI3K/AKT/mTOR signaling pathway in hepatocellular carcinoma cells. Our findings demonstrate that Artemisiae Iwayomogii Herba ethanol extract can efficiently induce apoptosis and inhibit the growth, migration, and invasion of human hepatocellular carcinoma cells, and simultaneously block PI3K/AKT/mTOR pathway. We therefore suggest Artemisiae Iwayomogii Herba ethanol extract as a novel natural agent for prevention and therapy of hepatocellular carcinoma.

Key words

Artemisiae Iwayomogii Herba - Artemisia gmelinii - Compositae - Apoptosis - hepatocellular carcinoma - PI3K
 

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