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

Juyoung Kim; Kyung Hee Jung; Jin Gyu Choi; Myung Sook Oh; Soon-Sun Hong

doi:10.1055/a-1167-4284

Planta Medica, Inhaltsverzeichnis

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‡

¹Department of Biomedical Sciences, College of Medicine, Inha University, Incheon, Korea

,

Kyung Hee Jung‡

¹Department of Biomedical Sciences, College of Medicine, Inha University, Incheon, Korea

,

Jin Gyu Choi‡

²Department of Oriental Pharmaceutical Science, College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, Seoul, Korea

,

Myung Sook Oh

²Department of Oriental Pharmaceutical Science, College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, Seoul, Korea

³Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, Korea

,

Soon-Sun Hong

¹Department of Biomedical Sciences, College of Medicine, Inha University, Incheon, Korea

› Institutsangaben

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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