PMID- 28440448 OWN - NLM STAT- MEDLINE DCOM- 20180306 LR - 20211204 IS - 1791-2431 (Electronic) IS - 1021-335X (Linking) VI - 37 IP - 6 DP - 2017 Jun TI - Modified Panax ginseng extract regulates autophagy by AMPK signaling in A549 human lung cancer cells. PG - 3287-3296 LID - 10.3892/or.2017.5590 [doi] AB - 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 microg/ml induced punctate cytoplasmic expression of LC3, Beclin-1 and ATG5 and increased expression of endogenous LC3-II whereas 50 microg/ml did not inhibit the proliferation of A549 cells. Compared to the control cells, in cells treated with MRGX at 100 microg/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. FAU - Yoo, Hwa-Seung AU - Yoo HS AD - East-West Cancer Center, Dunsan Oriental Hospital of Daejeon University, Daejeon 302-122, Republic of Korea. FAU - Kim, Jung Min AU - Kim JM AD - NAR Center, Inc. & Genoplan Korea, Inc., Seoul 06221, Republic of Korea. FAU - Jo, Eunbi AU - Jo E AD - Division of Bioconvergence Analysis, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea. FAU - Cho, Chong-Kwan AU - Cho CK AD - East-West Cancer Center, Dunsan Oriental Hospital of Daejeon University, Daejeon 302-122, Republic of Korea. FAU - Lee, Seung-Yeul AU - Lee SY AD - Division of Bioconvergence Analysis, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea. FAU - Kang, Hwan Su AU - Kang HS AD - Division of Bioconvergence Analysis, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea. FAU - Lee, Min-Goo AU - Lee MG AD - Department of Physiology, Korea University College of Medicine, Seoul 02841, Republic of Korea. FAU - Yang, Pei-Ying AU - Yang PY AD - Departments of Palliative, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. FAU - Jang, Ik-Soon AU - Jang IS AD - Division of Bioconvergence Analysis, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea. LA - eng PT - Journal Article DEP - 20170420 PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Beclin-1) RN - 0 (Cell Cycle Proteins) RN - 0 (EIF4EBP1 protein, human) RN - 0 (MAP1LC3A protein, human) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Phosphoproteins) RN - 0 (Plant Extracts) RN - 0 (Saponins) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - EC 2.7.11.31 (PRKAA1 protein, human) SB - IM MH - A549 Cells MH - AMP-Activated Protein Kinases/genetics MH - Adaptor Proteins, Signal Transducing/genetics MH - Autophagy/drug effects/*genetics MH - Beclin-1/genetics MH - Cell Cycle Proteins MH - Gene Expression Regulation, Neoplastic/drug effects MH - Humans MH - Lung Neoplasms/*drug therapy/genetics/pathology MH - Microtubule-Associated Proteins/genetics MH - Panax/chemistry MH - Phosphoproteins/genetics MH - Plant Extracts/*administration & dosage/chemistry MH - Saponins/genetics/metabolism MH - Signal Transduction/drug effects MH - TOR Serine-Threonine Kinases/genetics EDAT- 2017/04/26 06:00 MHDA- 2018/03/07 06:00 CRDT- 2017/04/26 06:00 PHST- 2016/08/04 00:00 [received] PHST- 2016/10/17 00:00 [accepted] PHST- 2017/04/26 06:00 [pubmed] PHST- 2018/03/07 06:00 [medline] PHST- 2017/04/26 06:00 [entrez] AID - 10.3892/or.2017.5590 [doi] PST - ppublish SO - Oncol Rep. 2017 Jun;37(6):3287-3296. doi: 10.3892/or.2017.5590. Epub 2017 Apr 20.