Acanthopanax senticosus Harms extract causes G0/G1 cell cycle arrest and autophagy via inhibition of Rubicon in human liver cancer cells

Kawano,Yutaka; Tanaka,Maki; Fujishima,Masaki; Okumura,Eri; Takekoshi,Hideo; Takada,Kohichi; Uehara,Osamu; Abiko,Yoshihiro; Takeda,Hidekatsu

doi:10.3892/or.2021.7948

Acanthopanax senticosus Harms extract causes G0/G1 cell cycle arrest and autophagy via inhibition of Rubicon in human liver cancer cells

Authors:
- Yutaka Kawano
- Maki Tanaka
- Masaki Fujishima
- Eri Okumura
- Hideo Takekoshi
- Kohichi Takada
- Osamu Uehara
- Yoshihiro Abiko
- Hidekatsu Takeda
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Affiliations: Department of Gastroenterology, Health Sciences University of Hokkaido Hospital, Sapporo, Hokkaido 002‑8072, Japan, Department of Clinical Laboratory Science, Health Sciences University of Hokkaido Hospital, Sapporo, Hokkaido 002‑8072, Japan, Production and Development Department, Sun Chlorella Co., Ltd., Kyoto 600‑8177, Japan, Department of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido 060‑8543, Japan, Division of Disease Control and Molecular Epidemiology, Department of Oral Growth and Development, School of Dentistry, Health Sciences University of Hokkaido, Tobetsu, Hokkaido 061‑0293, Japan, Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, Tobetsu, Hokkaido 061‑0293, Japan, Department of Physical Therapy, Sapporo Medical University School of Medicine, Sapporo, Hokkaido 060‑8543, Japan
Published online on: January 22, 2021 https://doi.org/10.3892/or.2021.7948
Pages: 1193-1201
Copyright: © Kawano et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acanthopanax senticosus (Rupr. et Maxim) Harms (ASH), also known as Siberian ginseng or eleuthero, is a hardy shrub native to China, Korea, Russia and the northern region of Japan. ASH is used for the treatment of several diseases such as heart disease, hypertension, rheumatoid arthritis, allergies, chronic bronchitis, diabetes and cancer. In the present study, the inhibitory effect of the root extract of ASH (ASHE) on HuH‑7 and HepG2 liver cancer cells was examined. ASHE suppressed liver cancer cell proliferation by inducing cell cycle arrest at the G0/G1 phase, as well as apoptosis, as indicated by the increased number of Annexin V and 7‑AAD‑positive cells. Furthermore, the expression of LC3‑II, an autophagy marker, in these cells also increased post treatment with ASHE. LC3‑II induction was further enhanced by co‑treatment with chloroquine. Fluorescence and transmission electron micrographs of ASHE‑treated liver cancer cells showed the presence of an increased number of autophagic vesicles. A decreased protein expression level of run domain Beclin‑1‑interacting and cysteine‑rich domain‑containing, an autophagy inhibitor, with no change in RUBCN mRNA expression was observed, indicating activation of the autophagosome‑lysosome fusion step of autophagy. In conclusion, ASHE exerts cytostatic activity on liver cancer cells via both apoptosis and autophagy, and may serve as a potential therapeutic agent for management of liver cancer and autophagy‑related diseases.

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