Modified Panax ginseng extract regulates autophagy by AMPK signaling in A549 human lung cancer cells

Yoo,Hwa-Seung; Kim,Jung Min; Jo,Eunbi; Cho,Chong-Kwan; Lee,Seung-Yeul; Kang,Hwan Su; Lee,Min-Goo; Yang,Pei-Ying; Jang,Ik-Soon

doi:10.3892/or.2017.5590

Modified Panax ginseng extract regulates autophagy by AMPK signaling in A549 human lung cancer cells

Authors:
- Hwa-Seung Yoo
- Jung Min Kim
- Eunbi Jo
- Chong-Kwan Cho
- Seung-Yeul Lee
- Hwan Su Kang
- Min-Goo Lee
- Pei-Ying Yang
- Ik-Soon Jang
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Affiliations: East-West Cancer Center, Dunsan Oriental Hospital of Daejeon University, Daejeon 302-122, Republic of Korea, NAR Center, Inc. & Genoplan Korea, Inc., Seoul 06221, Republic of Korea, Division of Bioconvergence Analysis, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea, Department of Physiology, Korea University College of Medicine, Seoul 02841, Republic of Korea, Departments of Palliative, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Published online on: April 20, 2017 https://doi.org/10.3892/or.2017.5590
Pages: 3287-3296

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Abstract

Panax ginseng has been used worldwide as a traditional medicine for the treatment of cancer and other diseases. The antiproliferative activity of ginseng has been increased after enzymatic processing of ginseng saponin, which may result in the accumulation of minor saponins, such as Rh2, Rg3, compound K and protopanaxatriol type (PPT) in modified regular ginseng extract (MRGX). In the present study, the anticancer activity and the associated mechanisms of MRGX were investigated using A549 human lung cancer cells. To elucidate the mechanisms underlying the effects of MRGX, we performed a microarray analysis of gene expression in the A549 cells. Molecular mechanisms that were associated with the anticancer activity of MRGX were studied, with a special focus on the autophagy-related multiple signaling pathways in lung cancer cells. Microarray analyses elucidated autophagy-related genes affected by MRGX. Administration of MRGX at 100 µg/ml induced punctate cytoplasmic expression of LC3, Beclin-1 and ATG5 and increased expression of endogenous LC3-II whereas 50 µg/ml did not inhibit the proliferation of A549 cells. Compared to the control cells, in cells treated with MRGX at 100 µg/ml, the level of p-Akt was increased, while that of mTOR-4EBP1 was decreased. Downregulation of mTOR and 4EBP1 in the MRGX-treated cells was found not to be a p-Ulk (S757)-dependent pathway, but a p-Ulk (S317)-dependent autophagic pathway, using AMPK. These data suggest that MRGX regulates AMPK and induces autophagy in lung cancer cells.

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